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

HRID 360031노트

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HRID 360031 반응식
[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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

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온도
-85 °C

실험 절차

Crude (R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3oxohexanoate, 21 g (0.0924 mol), is dissolved in 940 mL of tetrahydrofuran and 190 mL of methanol under a nitrogen atmosphere. This solution is cooled to -85° C. and 95 mL of a 15% solution of methoxydiethylborane in tetrahydrofuran is added. The reaction is cooled to -97° C. and 6.5 9 (0.172 mol) of sodium borohydride is added in 0.5 g portions over 1.5 hours. The reaction is maintained between -93° C. and -97° C. for 13 hours and allowed to warm to room temperature and stand for 60 hours under a nitrogen atmosphere. The reaction is quenched by the addition of 25 mL (0.395 mol) acetic acid and concentrated by vacuum distillation to an oil. The residue is dissolved with 500 mL methanol, concentrated by vacuum distillation, redissolved with 500 mL methanol and reconcentrated by vacuum distillation to give a dark brown oil. This oil is taken up in 500 mL of ethyl acetate and filtered through a plug of silica gel with the aid of 250 mL of ethyl acetate The solution is evaporated to give 15 g of crude [R-(R*,R*)]-1,1-dimethylethyl 6-cyano-3,5-dihydroxyhexanoate which is used without further purification.

후처리

  1. temperatureThe reaction is cooled to -97° C.
  2. temperatureThe reaction is maintained between -93° C. and -97° C. for 13 hours
  3. temperatureto warm to room temperature
  4. concentrationconcentrated by vacuum distillation to an oil
  5. dissolutionThe residue is dissolved with 500 mL methanol
  6. concentrationconcentrated by vacuum distillation
  7. dissolutionredissolved with 500 mL methanol
  8. distillationreconcentrated by vacuum distillation
  9. customto give a dark brown oil
  10. filtrationfiltered through a plug of silica gel with the aid of 250 mL of ethyl acetate The solution
  11. customis evaporated

출처 및 근거

ORD 기록
ord-e90a17898c6a4640ab16726c4bb0569a
출처 데이터셋
uspto-grants-1991_03
특허 번호
US05003080

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