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

HRID 277820

反応式

HRID 277820 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
-78 °C

実験手順

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 (1000 m silica gel rotor, ethyl acetate/hexane (20/80) eluent), mp 116-118° C.

後処理

  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

出典と根拠

ORDレコード
ord-61dbcf98539f4d4aacab1920fbaafc16
出典データセット
uspto-grants-2002_03
特許番号
US06358942B1

関連ノート

読み込み中…