Toluene → 1-(t-Butoxycarbonyl)-4-(3,3-difluoro-3-(4-fluorophenyl)prop-1-en-1-yl)piperidine

HRID 278229노트

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HRID 278229 반응식
[I-].[C:2]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([CH2:15][P+](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])([CH3:4])[CH3:3].C1(C)C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:52][C:53]([F:65])([C:58]1[CH:63]=[CH:62][C:61]([F:64])=[CH:60][CH:59]=1)[CH:54](OC)O>C1COCC1>[C:2]([O:6][C:7]([N:9]1[CH2:10][CH2:11][CH:12]([CH:15]=[CH:54][C:53]([F:65])([F:52])[C:58]2[CH:59]=[CH:60][C:61]([F:64])=[CH:62][CH:63]=2)[CH2:13][CH2:14]1)=[O:8])([CH3:3])([CH3:4])[CH3:5]

참가 물질

6

반응물 4

HCID 1140TolueneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 181874712,2-Difluoro-2-(4-fluorophenyl)-1-methoxyethanolHCID 18187633((1-(tert-Butoxycarbonyl)piperidin-4-yl)methyl)triphenylphosphonium iodide

생성물 1

HCID 543091291-(t-Butoxycarbonyl)-4-(3,3-difluoro-3-(4-fluorophenyl)prop-1-en-1-yl)piperidine수율 71.6%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A suspension of ((1-(t-butoxycarbonyl)piperidin-4-yl)methyl)triphenylphosphonium iodide (500 mg, 0,92 mmol) from Step C in THF (7.2 mL) was stirred at rt for 30 min. A 0.5 M toluene solution of potassium bis(trimethylsilyl)amide (1.8 mL, 0.90 mmol) was added over 3 min., giving an orange suspension. After 30 min., crude 2,2-difluoro-2-(4-fluorophenyl)-1-methoxyethanol (95 mg, 0.46 mmol) was added in THF (1.0 mL). After an additional 30 min, the mixture was quenched by the addition of saturated aq. NH4Cl (2 mL). The mixture was partitioned between ethyl acetate (50 mL) and water (75 mL), and the aqueous layer was extracted with ethyl acetate (50 mL). The organic layers were washed in succession with saturated aq. brine (25 mL), dried (sodium sulfate), decanted, and evaporated. The crude product was purified by FC, eluting with 10% ether in hexane to give 117 mg of the title compound as a 95:5 mixture of cis and trans isomers, respectively.

후처리

  1. customgiving an orange suspension
  2. waitAfter 30 min.
  3. waitAfter an additional 30 min
  4. customthe mixture was quenched by the addition of saturated aq. NH4Cl (2 mL)
  5. customThe mixture was partitioned between ethyl acetate (50 mL) and water (75 mL)
  6. extractionthe aqueous layer was extracted with ethyl acetate (50 mL)
  7. washThe organic layers were washed in succession with saturated aq. brine (25 mL)
  8. dry with materialdried (sodium sulfate)
  9. customdecanted
  10. customevaporated
  11. customThe crude product was purified by FC
  12. washeluting with 10% ether in hexane

출처 및 근거

ORD 기록
ord-a49074f86c484d29a6f836989b2a2977
출처 데이터셋
uspto-grants-2002_03
특허 번호
US06358979B1

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