Tetrabutylammonium Fluoride → 2-(R)-(3-(R)-(hydroxymethyl)4-(S)-phenylpyrrolidin-1-yl)-3-(cyclobutyl)propionic acid, benzyl ester

HRID 2185540ノート

反応式

HRID 2185540 の反応式
[Si]([O:8][CH2:9][C@@H:10]1[C@@H:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][N:12]([C@H:21]([CH2:32][CH:33]2[CH2:36][CH2:35][CH2:34]2)[C:22]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[O:23])[CH2:11]1)(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[OH:8][CH2:9][C@@H:10]1[C@@H:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:13][N:12]([C@H:21]([CH2:32][CH:33]2[CH2:34][CH2:35][CH2:36]2)[C:22]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)=[O:23])[CH2:11]1

参加物

4

反応物 2

HCID 2724141Tetrabutylammonium FluorideHCID 1317226812-(R)-(3-(R)-(t-Butyldimethylsilyloxymethyl)-4-(S)-phenyl-pyrrolidin1-yl)-3-(cyclobutyl)propionic acid, benzyl ester

生成物 1

HCID 1317226822-(R)-(3-(R)-(hydroxymethyl)4-(S)-phenylpyrrolidin-1-yl)-3-(cyclobutyl)propionic acid, benzyl ester収率 94.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of 3.20 g (6.3 mmol) of 2-(R)-(3-(R)-(t-butyldimethylsilyloxymethyl)-4-(S)-phenylpyrrolidin-1-yl)-3-(cyclobutyl) propionic acid, benzyl ester (from Step A) in 40 mL of THF at 0° C. was treated with 10 mL of 1.0 M tetrabutylammonium fluoride solution in THF. The resulting mixture was warmed to rt and stirred for 2.5 h. The reaction mixture was partitioned between 200 mL of ether and 100 mL of 50% sat'd NaHCO3 and the layers were separated. The organic layer was dried over MgSO4 and concentrated. Flash chromatography on 100 g of silica gel using 2:1 v/v hexanes/ether as the eluant afforded 2.34 g (94%) of the title compound: 1H NMR (500 MHz) δ1.56-2.07 (8H), 2.15 (br s, 1H), 2.27-2.37 (2H), 2.64 (t, J=11.0, 1H), 2.80 (dd, J=6.5, 11.0), 3.04-3.11 (2H), 3.23-3.30 (2H), 3.56 (dd, J=7.5, 13.0, 1H), 3.68 (dd, J=5.5, 13.0, 1H), 5.15 (ABq, J=20.0, 2H), 7.17-7.40 (10H).

後処理

  1. customThe reaction mixture was partitioned between 200 mL of ether and 100 mL of 50%
  2. customthe layers were separated
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated

出典と根拠

ORDレコード
ord-c30095d5fb4e42d1b9d43431ad2f5784
出典データセット
uspto-grants-2002_06
特許番号
US06399619B1

反応ノート

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