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

HRID 1062823

반응식

HRID 1062823 반응식
[C:1]([CH2:3][CH: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].C(O)(=O)C.[BH4-].[Na+].[OH-].[Na+]>O1CCCC1.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]

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 11637184Tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate

생성물 1

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

시약·촉매·용매 2

HCID 887Methanol용매2회HCID 8028Tetrahydrofuran용매

실험 절차

Crude 5R 1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxohexanoate (about 150 moles) from Step (1) is dissolved in the first distillate from Step (a) along with 50 L of tetrahydrofuran, cooled to −75° C.±20° C., and optionally diluted with 25 L of methanol, and 10 kg of acetic acid. Sodium borohydride (8 kg) as a solution in methanol and aqueous sodium hydroxide is added slowly. After the addition, the reaction mixture is warmed to 0° C.±25° C. The reaction mixture is quenched by the addition of 10 kg of acetic acid and 20 L of methanol and concentrated by vacuum distillation. The residue is dissolved in methanol and acetic acid, optionally diluted with water, and concentrated by vacuum distillation. The residue is dissolved in methanol and concentrated by vacuum distillation. The residue is dissolved in a mixture of water and ethyl acetate, and the aqueous layer separated. The organic layer is concentrated by vacuum distillation. The residue is dissolved in methanol and acetic acid and concentrated by vacuum distillation. The residue is dissolved in ethyl acetate and concentrated by vacuum distillation affording crude [R—(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate.

후처리

  1. temperaturecooled to −75° C.±20° C.
  2. additionAfter the addition
  3. temperaturethe reaction mixture is warmed to 0° C.±25° C
  4. customThe reaction mixture is quenched by the addition of 10 kg of acetic acid and 20 L of methanol
  5. concentrationconcentrated by vacuum distillation
  6. dissolutionThe residue is dissolved in methanol
  7. additionacetic acid, optionally diluted with water
  8. concentrationconcentrated by vacuum distillation
  9. dissolutionThe residue is dissolved in methanol
  10. concentrationconcentrated by vacuum distillation
  11. dissolutionThe residue is dissolved in a mixture of water and ethyl acetate
  12. customthe aqueous layer separated
  13. concentrationThe organic layer is concentrated by vacuum distillation
  14. dissolutionThe residue is dissolved in methanol
  15. concentrationacetic acid and concentrated by vacuum distillation
  16. dissolutionThe residue is dissolved in ethyl acetate
  17. concentrationconcentrated by vacuum distillation

출처 및 근거

ORD 기록
ord-ba9292c309024c0ebdb0fd1057be15e0
출처 데이터셋
uspto-grants-2005_11
특허 번호
US06962994B2

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