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Triethylamine → 2-oxo-2-phenylethyl (3R,4S)-4-allyl-3-azido-1-[N-benzyl-N-(tert-butoxycarbonyl)glycyl]pyrrolidine-3-carboxylate

HRID 61408
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HRID 61408 반응식
FC(F)(F)C(O)=O.[CH2:8]([C@H:11]1[CH2:15][NH:14][CH2:13][C@@:12]1([N:28]=[N+:29]=[N-:30])[C:16]([O:18][CH2:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:17])[CH:9]=[CH2:10].[CH2:31]([N:38]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][C:40](O)=[O:41])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.CCN(CC)CC.F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>C(Cl)Cl>[CH2:8]([C@H:11]1[CH2:15][N:14]([C:40](=[O:41])[CH2:39][N:38]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:43]([O:45][C:46]([CH3:49])([CH3:47])[CH3:48])=[O:44])[CH2:13][C@@:12]1([N:28]=[N+:29]=[N-:30])[C:16]([O:18][CH2:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:17])[CH:9]=[CH2:10]
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참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 105158162-(Benzyl(tert-butoxycarbonyl)amino)acetic acidHCID 131734495racemic 2-oxo-2-phenylethyl (3R,4S)-4-allyl-3-azidopyrrolidine-3-carboxylate trifluoroacetate

생성물 1

HCID 118216036
2-oxo-2-phenylethyl (3R,4S)-4-allyl-3-azido-1-[N-benzyl-N-(tert-butoxycarbonyl)glycyl]pyrrolidine-3-carboxylate
수율 65%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

A stirred mixture of the crude racemic 2-oxo-2-phenylethyl (3R,4S)-4-allyl-3-azidopyrrolidine-3-carboxylate trifluoroacetate (Step 1, ˜1 mmol) and N-benzyl-N-(tert-butoxycarbonyl)glycine (337 mg, 1.27 mmol) in methylene chloride (9 mL) was treated with Et3N (0.495 mL, 3.55 mmol) followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU, 502 mg, 1.32 mmol), and the resulting mixture was stirred at room temperature and monitored by HPLC. At 1 h, the reaction was diluted with methylene chloride (20 mL), washed with water (20 mL), 1N aqueous HCl (10 mL), saturated aqueous NaHCO3 (20 mL) and saturated aqueous sodium chloride (10 mL), dried over Na2SO4, and concentrated under reduced pressure. Purification by silica gel chromatography (40 g column, 15-30% ethyl acetate in hexanes) gave 2-oxo-2-phenylethyl (3R,4S)-4-allyl-3-azido-1-[N-benzyl-N-(tert-butoxycarbonyl)glycyl]pyrrolidine-3-carboxylate (365 mg, 64%) as an amber gum which was used as is in the next step. LC-MS ESI+MS found for C30H35N5O6 m/z 562.3 (M+H), 584.3 (M+Na), 1H NMR (CDCl3, 400 MHz) δ 7.92 (m, 2 H), 7.66 (m, 1 H), 7.53 (m, 2 H), 7.30 (m, 5 H), 5.75 (m, 1 H), 5.52 (m, 2 H), 5.12 (m, 2 H), 4.58 (m, 2 H), 4.22-3.42 (m, 6 H), 2.60 (m, 1 H), 2.50 (m, 1 H), 2.12 (m, 1 H), 1.48 (s, 9 H).

후처리

  1. washwashed with water (20 mL), 1N aqueous HCl (10 mL), saturated aqueous NaHCO3 (20 mL) and saturated aqueous sodium chloride (10 mL)
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customPurification by silica gel chromatography (40 g column, 15-30% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-7df8981707354bcc8ca054e4f7099a1a
출처 데이터셋
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09440995B2

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