Potassium tert-butoxide → tert-Butyl 2,2-difluoro-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 471049노트

반응식

HRID 471049 반응식
Br[C:2]([F:22])([F:21])[C:3]([NH:5][CH2:6][C:7]1([OH:20])[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]1)=[O:4].CC(C)([O-])C.[K+]>C1COCC1>[F:21][C:2]1([F:22])[C:3](=[O:4])[NH:5][CH2:6][C:7]2([CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)[O:20]1

참가 물질

4

반응물 2

HCID 23665647Potassium tert-butoxideHCID 57988980tert-Butyl 4-((2-bromo-2,2-difluoroacetamido)methyl)-4-hydroxypiperidine-1-carboxylate

생성물 1

HCID 57989103tert-Butyl 2,2-difluoro-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of tert-butyl 4-((2-bromo-2,2-difluoroacetamido)methyl)-4-hydroxypiperidine-1-carboxylate (example 37, step a) (3.2 g) in THF (40 mL) was added dropwise over 15 minutes to a stirred solution of potassium tert-butoxide (1M in t-butanol, 16.53 mL) and THF (60 mL) at 70° C. under nitrogen. At the end of the addition the mixture was heated for a further 10 minutes and then cooled to room temperature. The mixture was partitioned between ethyl acetate and brine, the organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 30% isohexane in ethyl acetate. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.55 g.

후처리

  1. additionAt the end of the addition the mixture
  2. temperaturewas heated for a further 10 minutes
  3. customThe mixture was partitioned between ethyl acetate and brine
  4. dry with materialthe organic layer was dried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent evaporated under reduced pressure
  7. customThe crude product was purified by flash silica chromatography
  8. customPure fractions were evaporated to dryness

출처 및 근거

ORD 기록
ord-f7fcc2248e7f413a9a54d7499ae4b8db
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629271B2

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