一、加料过程常用表述
1. 添加试剂
To a mixture (suspension / solution / slurry) ofcompound 12 (487 mg, 1 mmol) and o-plenylenediamine (648 mg, 6 mmol) inCH2Cl2(15 mL) being cooled to 0oC was addedthe DCC (226 mg, 1.1 mmol).
Anhydrous lithium iodide (1.38 g, 10.3 mmol) was added the five portions (dropwise/ in one portion / in portions) to a stirred solution of compound 12 (10.93 g, 51.5mmol) in CH2Cl2(120 mL).
A round-bottom flask was charged with compound 3 (1.75 g, 5.27 mmol), LiCl (1.17 g, 26.3 mmol), DMSO (100 mL) and H2O (378ul)
2. 催化量的
Et3N (20 mL, 142 mmol) and a catalytic amount of DMAP were added the solution of compound 1 (4.549 g, 46.4mmol) in CH2Cl2(120 mL) at 0oC
3.气体保护
To a stirred –78oC solution of trimethylsilyacetylene (4.44 g, 45.5 mmol) in THF (10 mL) under Argon wasadded dropwise n-butylithium (1.6 M in hexane, 28.25 mL).
4. 通入气体
An ozone-enriched steam of oxygen was bubbled througha cold (-78oC) solution of compound 9 (128 mg, 1.409 mmol) in CH2Cl2 (5 mL) untilit turned light blue. The solution was purged with argon at -78oCfor 10 min to remove the excess O3.
5. 通过双针头导管加料
The mixture was added to a solution of compound 2 (3.00 g, 12.8 mmol) in THF (48mL) via cannula over a period of 30 min.
A solution of compound 29 (100 mg, 0.19 mmol, 1.0 equiv) in dry DMSO (1.5 mL) wascannulated under Argon to a vigorously stirred mixture of powered potassiumsuperoxide (62 mg, 0.87 mmol, 4.5 equiv) and 18-crown-6-ether (23 mg, 0.087mmol, 0.45 equiv) in dry DMSO (0.5 mL).
6. 通过注射器加料
To a stirred solution of compound 15 (8.61 g, 21.2 mmol)was added a solution of p-toluenesulfonicacid (6.0 g) in CH2Cl2via syringe over 5 min.
二、反应过程常用表述
1. 反应检测
After 1 h, TLC analysis (CH2Cl2/ hexane 3:1) showed the complete consumption of compound 15.
2. 放置过夜
The mixture was left standing overnight.
3. 甲苯/乙醇带水
Compound A(1.97 g, 6.63 mmol) was coevaporated with toluene five times to remove the water. The residue was subjected to toluene azeotrope to givethe corresponding acid chloride as brown oil. The aqueous portion was concentrated underreduced pressure followed by azeotropic removal of water with absolute EtOH
4. 氢化反应
A mixture of compound 1 (190 g, 0.88mmol) and Raney Ni (20 g) inethanol (1500 mL) and ethyl acetate (500 mL) was stirred under 1 atm at room temperaturefor an hour.
5. 分水器
A mixture of TsOH.H2O (56.91 g, 0.3 mol) and toluene (400 mL) was heated to reflux to remove water by Dean-Stark trap.
6. 反应放热
The reaction was exothermic.
7. 微波反应
The sealed vial was irradiated in the microwave on a Biotage Smith Synthesis at 150oC for 10 min.
三、后处理过程常用表述
1. 过滤
The mixture was filtered through a Celite pad, and thefiltrate was concentrated to give the crude product.
2. 淬灭
The reaction mixture was quenched by the addition of thesaturated aqueous NH4Cl.
3. 磨碎
The residue was triturated with ether and filtered to afforda white solid.
4. 在两相中分开
The residue was partitioned between ethyl acetate (100mL) and HCl (1 M aq., 50mL). The organic layer was washed with water, dried (MgSO4) andevaporated to dryness. Ethyl acetate (100 mL) and HCl (1 M aq., 50 mL) were added to the residue,and the layers were separated.
5. 静止固化
The crude product was purified by prep-HPLC to givecompound 4as colorless thick oil,which was solidified on standing.
6. 在冻干机冻干
The white solid was re-crystallized from water, driedby hyophilization to give a white solid.
7. 纯化
过柱：The crude product was chromatographed on silica gel(CH2Cl2 / MeOH 20:1→10:1→5:1) to give the compound 8 (0.282 g,51%) as a white solid. The crude product was purified by column chromatographyon silica gel eluted with (CH2Cl2 / MeOH，20:1→10:1→5:1) to give the compound 8 (0.282 g, 51%) as a white solid.
制备HPLC纯化
be purified by prep-HPLC to afford/give/yield
制备TLC纯化
be purified by prepare TLC to afford/give/yield
重结晶
recrystallized from
8. 调 pH
The pH was adjusted to around 9 by progressivelyadding solid NaHCO3
The mixture was adjusted to pH 9 with solid NaHCO3
9. 萃取
The aqueous layer was extracted with ethyl acetate (100mL × 4).
10. 浓缩
The mixture was evaporated to afford the crudeproduct.
The mixture was concentrated afford the crude product.
The solvent was removed to afford the crude product.
11. 干燥
干燥：The organic layer was dried over MgSO4, andconcentrated.
真空干燥：The precipitate was filtered and dried in vacuo (in/ undervacumm; under reduced pressure).
四、部分常见反应现象描述
1. 加料放热
A gentle reflux appeared throughout the addition
Heat generated during the addition.
The temperature was increased from 25oC to50oC during the addition.
2. 反应过程中或者降温有固体析出
Solid was precipitate out after 1h reaction.
The reaction mixture was cooled to -10oC,and solid was precipitate out.
3. 加料不溶解
XX was added to the mixture, and the resultingsuspension was stirred for 2hrs.
4. 加热溶解
The suspension was heated to 90oC andstirred until all solid was dissolved.
5. 反应变粘稠/变色
The reaction mixture became sticky after 2hrsreaction/stirring.
After 2hrs stirring, the mixture turned intoblack/brown/gray/yellow/red color.
五、特殊结果叙述
1. 无进一步处理
No further operation
2. 统一和其他批次一起后处理
The work-up of this batch was together with the otherbatches that recorded in the following pages.
3. 检测条件，不需要后处理
IPC check showed this condition is better/bad for thisreaction. No further operation forcondition screen reaction.
六、一些易错写法
|
Right（正确） |
Wrong（错误） |
|
pH |
PH |
|
m-CPBA |
MCPBA |
|
1HNMR |
HNMR |
|
mL |
ml |