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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
ノート
印刷プレビュー

反応式

HRID 61408 の反応式
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]
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-7df8981707354bcc8ca054e4f7099a1a
出典データセット
uspto-grants-2016_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09440995B2

反応ノート

読み込み中…

このページの内容参加物実験手順後処理出典と根拠反応ノート