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 590699

반응식

HRID 590699 반응식
[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]

참가 물질

6

반응물 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

생성물 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-carboxylate수율 82.5%

시약·촉매·용매 3

HCID 742671,2-Bis(diphenylphosphino)ethane촉매HCID 86594784Chloro-1,5-cyclooctadiene iridium촉매HCID 6344Dichloromethane용매

반응 조건

온도
-20 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-c0529111b9e0413fba81ba534427e210
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233985B2

연결된 노트

불러오는 중…