硼酸三甲酯 → (alphaR)-2-Bromo-5-chloro-alpha-methylbenzenemethanol

HRID 644951

反应方程式

HRID 644951 反应方程式
COB(OC)OC.C1(C(C2C=CC=CC=2)([C@@H]2CCCN2)O)C=CC=CC=1.[Br:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C:35](=[O:37])[CH3:36]>O1CCCC1>[Br:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][C:29]=1[C@H:35]([OH:37])[CH3:36]

参与物

5

反应物 3

HCID 8470硼酸三甲酯HCID 2724899(S)-(+)-alpha,alpha-二苯基脯氨醇HCID 124866172-溴-5-氯苯乙酮

产物 1

HCID 50852803(alphaR)-2-Bromo-5-chloro-alpha-methylbenzenemethanol

试剂、催化剂与溶剂 1

HCID 8028四氢呋喃溶剂2 次

反应条件

温度
0 °C

实验过程

Trimethylborate (1.74 mL, 15.4 mmol) was added to a stirred solution of (S)-(−)-alpha,alpha-diphenyl-2-pyrrolidinemethanol (3.24 g, 12.8 mol) in tetrahydrofaran (350 mL) at room temperature. After 1.25 h, borane-methyl sulfide complex (70.4 mL of a 2M solution in tetrahydrofuran, 0.141 mol) was added slowly and a gentle effervesence was observed. The resulting soution was cooled to approximately 0° C. and a solution of 1-(2-bromo-5-chlorophenyl)ethanone (˜30.0 g, 0.128 mmol) in tetrahydrofuran (150 mL) was then added uniformly over 1 h. After the addition, the resulting mixture was allowed to warm to ambient temperature and aged overnight. The reaction mixture was concentrated under reduced pressure to approximately one quarter of its original volume, poured into 1N hydrochloric acid and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (9% ethyl acetate/hexanes as eluent) afforded the title compound as a colorless solid (98:2 enantiomer ratio).

后处理

  1. additionAfter the addition
  2. temperatureto warm to ambient temperature and aged overnight
  3. concentrationThe reaction mixture was concentrated under reduced pressure to approximately one quarter of its original volume
  4. additionpoured into 1N hydrochloric acid
  5. extractionextracted three times with ethyl acetate
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification of the crude residue by flash chromatography on silica gel (9% ethyl acetate/hexanes as eluent)

来源与证据

ORD记录
ord-15b34e9762014b7f966ed7ebc5d8bf02
来源数据集
uspto-grants-2010_04
专利号
US07700778B2

关联笔记

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