Sodium borohydride → 1,1-Dimethylethyl 6-cyano-3,5-dihydroxyhexanoate

HRID 1062824노트

반응식

HRID 1062824 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].[BH4-].[Na+]>C(B(CC)CC)C.C1COCC1.CO.COCCOCCOCCOC>[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 2

HCID 4311764Sodium borohydrideHCID 11637184Tert-butyl 6-cyano-5-hydroxy-3-oxohexanoate

생성물 1

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

시약·촉매·용매 4

HCID 887Methanol용매HCID 7357Triethylborane용매HCID 8028Tetrahydrofuran용매2회HCID 8189Triglyme용매

실험 절차

Crude 5R 1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxohexanoate (about 130 mmoles) from Step (1) is dissolved in 100 mL 1 M triethylborane in THF and 65 mL tetrahydrofuran, stirred for about 2 hours at room temperature, then cooled to −75° C.±20° C., and diluted with 25 mL methanol. Sodium borohydride (6 g) as a solution in triglyme (75 mL) is added slowly. After the addition, the reaction mixture is warmed to 20° C. to 25° C. The reaction mixture is quenched by the addition of 20 mL methanol and 8 g acetic acid and concentrated by vacuum distillation—saving the distillate. The residue is diluted with 100 mL water and 200 mL ethyl acetate, agitated, and the phases separated. The organic layer is concentrated by vacuum distillation—keeping this distillate separate from the first one. The residue is dissolved in 200 mL methanol and 10 mL acetic acid and concentrated by vacuum distillation. The residue is dissolved in 200 mL methanol and concentrated by vacuum distillation. The residue is dissolved in 200 mL methanol and concentrated by vacuum distillation. The residue is dissolved in ethyl acetate and concentrated by vacuum distillation resulting in 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 20° C. to 25° C
  4. customThe reaction mixture is quenched by the addition of 20 mL methanol and 8 g acetic acid
  5. concentrationconcentrated by vacuum distillation—saving the distillate
  6. additionThe residue is diluted with 100 mL water and 200 mL ethyl acetate
  7. customthe phases separated
  8. concentrationThe organic layer is concentrated by vacuum distillation—keeping
  9. customthis distillate separate from the first one
  10. dissolutionThe residue is dissolved in 200 mL methanol
  11. concentration10 mL acetic acid and concentrated by vacuum distillation
  12. dissolutionThe residue is dissolved in 200 mL methanol
  13. concentrationconcentrated by vacuum distillation
  14. dissolutionThe residue is dissolved in 200 mL methanol
  15. concentrationconcentrated by vacuum distillation
  16. dissolutionThe residue is dissolved in ethyl acetate
  17. concentrationconcentrated by vacuum distillation

출처 및 근거

ORD 기록
ord-f7c329535e1e469a8b4b83a062b70a08
출처 데이터셋
uspto-grants-2005_11
특허 번호
US06962994B2

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