2,2,2-Trifluoroethanol → rel-(3R,4S)-tert-Butyl 3-acetamido-4-allyl-3-(tert-butylcarbamoyl)pyrrolidine-1-carboxylate

HRID 61354

반응식

HRID 61354 반응식
[CH2:1]([CH:4]1[C:8](=O)[CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1)[CH:2]=[CH2:3].[C:17]([O-:20])(=O)[CH3:18].[NH4+:21].[C:22]([N+:26]#[C-])([CH3:25])([CH3:24])[CH3:23].FC(F)(F)[CH2:30][OH:31]>>[C:17]([NH:21][C@:8]1([C:30](=[O:31])[NH:26][C:22]([CH3:25])([CH3:24])[CH3:23])[C@@H:4]([CH2:1][CH:2]=[CH2:3])[CH2:5][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7]1)(=[O:20])[CH3:18]

참가 물질

5

반응물 4

HCID 64092,2,2-TrifluoroethanolHCID 23577Tert-Butyl isocyanideHCID 517165Ammonium AcetateHCID 67513550Tert-butyl 3-allyl-4-oxopyrrolidine-1-carboxylate

생성물 1

HCID 69669632rel-(3R,4S)-tert-Butyl 3-acetamido-4-allyl-3-(tert-butylcarbamoyl)pyrrolidine-1-carboxylate

실험 절차

A stirred mixture of tert-butyl 3-allyl-4-oxopyrrolidine-1-carboxylate (13.23 g, 58.7 mmol) and ammonium acetate (11.95 g, 155 mmol) in 2,2,2-trifluoroethanol (25 mL) under nitrogen was treated with t-butylisonitrile (12.25 mL, 106 mmol), then stirred at room temperature for 4 days and concentrated. The residue was partitioned between water (100 mL) and methylene chloride (200 mL), and the aqueous layer was extracted with methylene chloride (2×75 mL). The combined organic solution was washed with water and saturated aqueous sodium chloride (100 mL each), dried (Na2SO4), and concentrated to an off-white solid. This was recrystallized twice with ethyl acetate (150 mL each) to afford a portion of the title product (8.36 g) as a white solid. The combined mother liquors were concentrated, dissolved in minimum methylene chloride, and loaded onto a silica gel column (650 mL volume). This was eluted with 60%, then 70%, then 90% ethyl acetate/heptane to afford additional product (3.84 g). Total yield of (3R,4S)-tert-butyl 3-acetamido-4-allyl-3-(tert-butylcarbamoyl)pyrrolidine-1-carboxylate was 12.22 g (57%) as a white solid. NMR (CDCl3) δ 6.30-6.70 (m, 2 H), 5.60-5.75 (m, 1 H), 4.95-5.10 (m, 2 H), 3.94 (d, J=11.5 Hz, 1 H), 3.75 (d, J=11.5 Hz, 1 H), 3.60 (m, 1 H), 3.00-3.20 (m, 2 H), 2.20-2.30 (m, 1 H), 2.00 (s, 3 H), 1.80-1.90 (m, 1 H), 1.44 (s, 9 H), 1.33 (s, 9 H). MS (m+1): 368.3; MS (m−bu+1): 312.1; MS (m−boc+1): 268.3.

후처리

  1. concentrationconcentrated
  2. customThe residue was partitioned between water (100 mL) and methylene chloride (200 mL)
  3. extractionthe aqueous layer was extracted with methylene chloride (2×75 mL)
  4. washThe combined organic solution was washed with water and saturated aqueous sodium chloride (100 mL each)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to an off-white solid
  7. customThis was recrystallized twice with ethyl acetate (150 mL each)

출처 및 근거

ORD 기록
ord-02d031e111c3459d83e77e68846588cd
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09440995B2

연결된 노트

불러오는 중…