(Diethylamino)sulfur trifluoride → 4-Fluoro-4-[4-[[(phenylmethoxy)carbonyl]amino]-2-fluorophenyl]-1-piperidinecarboxylic acid phenylmethyl ester

HRID 1740173

반응식

HRID 1740173 반응식
C(N(S(F)(F)[F:7])CC)C.[C:10]1([CH2:16][O:17][C:18]([N:20]2[CH2:25][CH2:24][C:23](O)([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([O:35][CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[O:34])=[CH:28][C:27]=3[F:43])[CH2:22][CH2:21]2)=[O:19])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O>[C:10]1([CH2:16][O:17][C:18]([N:20]2[CH2:25][CH2:24][C:23]([F:7])([C:26]3[CH:31]=[CH:30][C:29]([NH:32][C:33]([O:35][CH2:36][C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)=[O:34])=[CH:28][C:27]=3[F:43])[CH2:22][CH2:21]2)=[O:19])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

참가 물질

6

반응물 3

HCID 123472(Diethylamino)sulfur trifluorideHCID 516892Sodium BicarbonateHCID 542846344-Hydroxy-4-[2-fluoro-4-[[(phenylmethoxy)carbonyl]amino]phenyl]-1-piperidinecarboxylic acid phenylmethyl ester

생성물 1

HCID 538510694-Fluoro-4-[4-[[(phenylmethoxy)carbonyl]amino]-2-fluorophenyl]-1-piperidinecarboxylic acid phenylmethyl ester

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

반응 조건

온도
-78 °C

실험 절차

To a solution of diethylaminosulfur trifluoride (DAST, 0.65 mL) in dry methylene chloride (49 mL) at -78° C. under N2 is added a solution of 4-hydroxy-4-[4-[[(phenylmethoxy)carbonyl]amino]-2-fluorophenyl]-1-piperidinecarboxylic acid phenylmethyl ester (EXAMPLE 74, Step 1, 2.25 g) in dry methylene chloride (47 mL) over 2 mins. The resulting mixture is stirred at -78° C. for 1 hr and at ambient temperature for 30 mins and is then adjusted to pH 8 with saturated aqueous sodium bicarbonate (50 mL), diluted with water (50 mL), and the layers are separated. The organic phase is washed with water (25 mL) and saline (25 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue is chromatographed on silica gel (230-400 mesh, 150 g), eluting with methanol/methylene chloride (0.5/99.5). Those fractions with an Rf =0.27 by TLC (ethyl acetate/hexane, 25/75) are pooled and concentrated to give the title compound (contaminated with approx. 15% of the elimination side product). An analytical sample is prepared by radial chromatography (1000μ silica gel rotor, ethyl acetate/hexane (20/80) eluent), mp 116-118° C.

후처리

  1. customthe layers are separated
  2. washThe organic phase is washed with water (25 mL) and saline (25 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customthe residue is chromatographed on silica gel (230-400 mesh, 150 g)
  6. washeluting with methanol/methylene chloride (0.5/99.5)
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-e39e45f2516f44abb03960876bdb6625
출처 데이터셋
uspto-grants-1999_10
특허 번호
US05968962

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