Acetic Acid → 1,1-Dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

HRID 610635

反応式

HRID 610635 の反応式
[C:1]([CH2:3][C@@H:4]([OH:16])[CH2:5][C:6](=[O:15])[CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])#[N:2].COB(CC)CC.[BH4-].[Na+].C(O)(=O)C>O1CCCC1.C(OCC)(=O)C.CO>[C:1]([CH2:3][CH:4]([OH:16])[CH2:5][CH:6]([OH:15])[CH2:7][C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])#[N:2]

参加物

8

反応物 4

HCID 176Acetic AcidHCID 522516DiethylmethoxyboraneHCID 4311764Sodium borohydrideHCID 9794547tert-Butyl (R)-6-Cyano-5-hydroxy-3-oxohexanoate

生成物 1

HCID 222829971,1-Dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-85 °C

実験手順

Crude (5R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxo-hexanoate (Example 4), approximately 52 mol, was dissolved in 90 L of tetrahydrofuran and 19 L of methanol under a nitrogen atmosphere. This solution was cooled to -85° C. and 24 L of a 50% solution of methoxy-diethylborane in tetrahydrofuran was added. The reaction was cooled to -97° C. and 3.6 kg (126 mol) of sodium borohydride was added in 0.2 kg portions over 3 hours. The reaction was maintained between -93° C. and -85° C. for 5 hours and allowed to warm to room temperature and stand for 10 hours under a nitrogen atmosphere. The reaction was quenched by the addition of 7.5 L (118.5 mol) acetic acid and concentrated by vacuum distillation to an oil. The residue was dissolved with 40 L of methanol, concentrated by vacuum distillation, redissolved with 44 L of methanol, and reconcentrated by vacuum distillation to give a brown oil. This oil was taken up in 90 L of ethyl acetate and washed with 30 L of deionized water. The ethyl acetate solution was concentrated by vacuum distillation to give the title compound, [R-(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate, which was used without further purification.

後処理

  1. temperatureThe reaction was cooled to -97° C.
  2. temperatureThe reaction was maintained between -93° C. and -85° C. for 5 hours
  3. temperatureto warm to room temperature
  4. concentrationconcentrated by vacuum distillation to an oil
  5. dissolutionThe residue was dissolved with 40 L of methanol
  6. concentrationconcentrated by vacuum distillation
  7. dissolutionredissolved with 44 L of methanol
  8. distillationreconcentrated by vacuum distillation
  9. customto give a brown oil
  10. washwashed with 30 L of deionized water
  11. concentrationThe ethyl acetate solution was concentrated by vacuum distillation

出典と根拠

ORDレコード
ord-523fde3fbd5543f9b3e40a6680160a96
出典データセット
uspto-grants-1999_12
特許番号
US05998633

関連ノート

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