4,4,5,5-Tetramethyl[1,3,2]dioxaborolane → (3R,4S)-tert-butyl 3-acetamido-3-(tert-butylcarbamoyl)-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-1-carboxylate

HRID 61355

反応式

HRID 61355 の反応式
[C:1]([NH:4][C@:5]1([C:20](=[O:26])[NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C@@H:9]([CH2:10][CH:11]=[CH2:12])[CH2:8][N:7]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:6]1)(=[O:3])[CH3:2].[CH3:27][C:28]1([CH3:35])[C:32]([CH3:34])([CH3:33])[O:31][BH:30][O:29]1>C(Cl)Cl.[Ir].ClC1CCC=CCCC=1.C1(P(C2C=CC=CC=2)CCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([NH:4][C@:5]1([C:20](=[O:26])[NH:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C@@H:9]([CH2:10][CH2:11][CH2:12][B:30]2[O:31][C:32]([CH3:34])([CH3:33])[C:28]([CH3:35])([CH3:27])[O:29]2)[CH2:8][N:7]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[CH2:6]1)(=[O:3])[CH3:2]

参加物

6

反応物 2

HCID 27347684,4,5,5-Tetramethyl[1,3,2]dioxaborolaneHCID 69669632rel-(3R,4S)-tert-Butyl 3-acetamido-4-allyl-3-(tert-butylcarbamoyl)pyrrolidine-1-carboxylate

生成物 1

HCID 67517991(3R,4S)-tert-butyl 3-acetamido-3-(tert-butylcarbamoyl)-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-1-carboxylate収率 82.5%

試薬・触媒・溶媒 3

HCID 742671,2-Bis(diphenylphosphino)ethane触媒HCID 86594784Chloro-1,5-cyclooctadiene iridium触媒HCID 6344Dichloromethane溶媒

反応条件

温度
-20 °C

実験手順

A stirred solution of (3R,4S)-tert-butyl 3-acetamido-4-allyl-3-(tert-butylcarbamoyl)pyrrolidine-1-carboxylate (5.51 g, 15 mmol) in anhydrous methylene chloride (80 mL) under nitrogen was treated with chloro-1,5-cyclooctadiene iridium dimer (0.252 g, 0.375 mmol) and 1,2-bis(diphenylphosphino)ethane (0.299 g, 0.75 mmol), stirred for 30 min. and cooled (−20° C.). 4,4,5,5-Tetramethyl-1,3,2-dioxaborolane (3.30 mL, 22.5 mmol) was added dropwise, and the solution was placed in an ice bath and allowed to reach room temperature overnight (18 h). The mixture was quenched with water (75 mL), stirred 15 min, and extracted with ethyl acetate (400 mL, then 2×100 mL). The combined organic solution was washed with saturated aqueous sodium chloride (150 mL), dried (MgSO4), and concentrated. The solid was recrystallized (2 crops) from acetonitrile to afford (3R,4S)-tert-butyl 3-acetamido-3-(tert-butylcarbamoyl)-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl)pyrrolidine-1-carboxylate (6.13 g, 82%) as a white solid. NMR (CDCl3) δ 6.40-6.60 (m, 1 H), 6.23 (s, 1 H), 3.95-4.05 (m, 1 H), 3.65-3.75 (m, 2 H), 2.90-3.20 (m, 2 H), 2.00 (s, 3 H), 1.45 (s, 9 H), 1.30-1.45 (m, 4 H), 1.33 (s, 9 H), 1.22 (s, 12 H), 0.70-0.80 (m, 2 H). MS (m+1): 496.4.

後処理

  1. customthe solution was placed in an ice bath
  2. waitto reach room temperature overnight
  3. custom(18 h)
  4. customThe mixture was quenched with water (75 mL)
  5. stirringstirred 15 min
  6. extractionextracted with ethyl acetate (400 mL
  7. washThe combined organic solution was washed with saturated aqueous sodium chloride (150 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe solid was recrystallized (2 crops) from acetonitrile

出典と根拠

ORDレコード
ord-5647829d1be340b6902342f9d6832a3f
出典データセット
uspto-grants-2016_09
特許番号
US09440995B2

関連ノート

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