Imidazole → (3R,4R)-3-[1-(2-imidazol-1-yl-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1531501ノート

反応式

HRID 1531501 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[CH:16][CH:15]=2)[C@@H:10]([O:34][CH2:35][C:36]2[CH:45]=[C:44]3[C:39]([CH2:40][CH2:41][CH2:42][N:43]3[CH2:46][CH2:47]OS(C)(=O)=O)=[CH:38][CH:37]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:53]1[CH:57]=[CH:56][N:55]=[CH:54]1>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH2:21][CH2:22][CH2:23][O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[CH:18][CH:19]=2)[C@@H:10]([O:34][CH2:35][C:36]2[CH:37]=[C:38]3[C:39]([CH2:40][CH2:41][CH2:42][N:43]3[CH2:46][CH2:47][N:53]3[CH:57]=[CH:56][N:55]=[CH:54]3)=[CH:44][CH:45]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

参加物

4

反応物 2

HCID 795ImidazoleHCID 86756516(3R,4R)-3-[1-(2-methanesulfonyloxy-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 69488647(3R,4R)-3-[1-(2-imidazol-1-yl-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester収率 31.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution of 0.220 g (0.298 mmol) (3R,4R)-3-[1-(2-methanesulfonyloxy-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester [example 9(a)] and 0.30 g (0.446 mmol, 1.50 equiv.) of imidazole in 1.8 ml of absolute N,N-dimethylformamide was stirred for 4 h at 80° C. The reaction was allowed to warm to room temperature, poured into 50 ml of an ice/water mixture and extracted three times with 50 ml of diethyl ether. The combined organic phases were washed twice with 20 ml of water, evaporated under reduced pressure and dried in a high vacuum. The thus obtained crude product was purified by chromatography on silica gel using a 20:1 v/v mixture of dichloromethane/methanol as the eluent to yield 0.067 g (0.094 mmol, 31.5% of theory) of (3R,4R)-3-[1-(2-imidazol-1-yl-ethyl)-1,2,3,4-tetrahydro-quinolin-7-ylmethoxy]-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylic acid tert-butyl ester as a light yellow oil; MS: 711 (M+H)+.

後処理

  1. extractionextracted three times with 50 ml of diethyl ether
  2. washThe combined organic phases were washed twice with 20 ml of water
  3. customevaporated under reduced pressure
  4. customdried in a high vacuum
  5. customThe thus obtained crude product
  6. customwas purified by chromatography on silica gel using
  7. additiona 20:1 v/v mixture of dichloromethane/methanol as the eluent

出典と根拠

ORDレコード
ord-a7e1d2a4c93445129cf63c2121258790
出典データセット
uspto-grants-2001_03
特許番号
US06197959B1

反応ノート

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