Pyridine → (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (E)-3-(3,4-difluorophenyl)-2-propenoate

HRID 130590

반응식

HRID 130590 반응식
[CH3:1][C@H:2]1[CH2:7][C@@H:6]([OH:8])[C@H:5]([CH:9]([CH3:11])[CH3:10])[CH2:4][CH2:3]1.[F:12][C:13]1[CH:14]=[C:15](/[CH:20]=[CH:21]/[C:22](Cl)=[O:23])[CH:16]=[CH:17][C:18]=1[F:19].N1C=CC=CC=1>C1(C)C=CC=CC=1>[F:12][C:13]1[CH:14]=[C:15](/[CH:20]=[CH:21]/[C:22]([O:8][C@@H:6]2[CH2:7][C@H:2]([CH3:1])[CH2:3][CH2:4][C@H:5]2[CH:9]([CH3:11])[CH3:10])=[O:23])[CH:16]=[CH:17][C:18]=1[F:19]

참가 물질

5

반응물 3

HCID 1049PyridineHCID 16666(-)-MentholHCID 9920680(2E)-3-(3,4-Difluorophenyl)-2-propenoyl chloride

생성물 1

HCID 10268077(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (E)-3-(3,4-difluorophenyl)-2-propenoate

시약·촉매·용매 1

HCID 1140Toluene용매2회

반응 조건

온도
65 °C

실험 절차

A solution of L-menthol (7.1 kg) in toluene (8.5 kg) was added over a 20 minute period to the solution of (E)-3-(3,4-difluorophenyl)-2-propenoyl chloride (prepared as in Step 2) and pyridine (0.18 kg, 2.28 mol) stirring at 65° C. The reaction mixture was stirred at 65° C. for a further 4 hours and 40 minutes after the addition was complete, then cooled to 25° C. and stirred for a 14 hours. The solution was diluted with toluene (16 kg), washed with 5% aqueous sodium chloride (6.4 kg), then 6% sodium hydrogen carbonate (6.47 kg), then water (6.1 kg). The solution was dried azeotropically by distillation of the solvent (20 L) under reduced pressure. Dimethyl sulfoxide (33.9 kg) was added and the remaining toluene was distilled off under reduced pressure, affording 47.3 kg of a solution of (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (E)-3-(3,4-difluorophenyl)-2-propenoate (approx. 13.3 kg) in dimethyl sulfoxide.

후처리

  1. stirringThe reaction mixture was stirred at 65° C. for a further 4 hours and 40 minutes
  2. additionafter the addition
  3. temperaturecooled to 25° C.
  4. stirringstirred for a 14 hours
  5. washwashed with 5% aqueous sodium chloride (6.4 kg)
  6. dry with materialThe solution was dried azeotropically by distillation of the solvent (20 L) under reduced pressure
  7. additionDimethyl sulfoxide (33.9 kg) was added
  8. distillationthe remaining toluene was distilled off under reduced pressure

출처 및 근거

ORD 기록
ord-621b09b53e5044528fb29f1328e9c063
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07381828B2

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