1,1'-Carbonyldiimidazole → (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl-N-[(1S,2R)-3-chloro-1-benzyl-2-hydroxypropyl]carbamate

HRID 73815노트

반응식

HRID 73815 반응식
[C:1](N1C=CN=C1)(N1C=CN=C1)=[O:2].[O:13]1[C@H:17]2[O:18][CH2:19][CH2:20][C@H:16]2[C@@H:15]([OH:21])[CH2:14]1.Cl.[NH2:23][C@@H:24]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C@H:25]([OH:28])[CH2:26][Cl:27].N[C@@H](CC1C=CC=CC=1)[C@H](O)CCl>C1COCC1.C(OCC)(=O)C>[O:13]1[C@H:17]2[O:18][CH2:19][CH2:20][C@H:16]2[C@@H:15]([O:21][C:1](=[O:2])[NH:23][C@@H:24]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C@@H:25]([OH:28])[CH2:26][Cl:27])[CH2:14]1

참가 물질

7

반응물 4

HCID 682631,1'-CarbonyldiimidazoleHCID 9942150(3R,3aS,6aR)-hexahydrofuro(2,3-b)furan-3-olHCID 11183945(2S,3S)-3-amino-1-chloro-2-hydroxy-4-phenylbutaneHCID 46703513(2S,3S)-3-Amino-1-chloro-4-phenylbutan-2-ol hydrochloride

생성물 1

HCID 86674032(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl-N-[(1S,2R)-3-chloro-1-benzyl-2-hydroxypropyl]carbamate

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

실험 절차

1,1′-carbonyldiimidazole (162.15 g, 1 mol) was added to THF (0.5 L), following by solution of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol (135.2 g, 1.04 mol) in 0.3 L of THF and the mixture was stirred for a further hour. (2S,3S)-3-amino-1-chloro-2-hydroxy-4-phenylbutane hydrochloride (229 g, 0.97 mol) was added and the mixture heated at 55-60° C. approximately 5-6 hours under TLC control (for complete disappearance of (2S,3S)-3-amino-1-chloro-2-hydroxy-4-phenylbutane). After completion of reaction the solution was cooled and transformed to the next step. For the preparation of analytical sample, 10 ml of solution was diluted with 50 ml of ethyl acetate, washed with water (40 mL), diluted hydrochloric acid (40 ml), 5% aqueous sodium hydrogen carbonate (40 mL) and water (50 mL). The solution was dried over sodium sulfate and evaporated to dryness. MS: m/z 356 (MH+). NMR spectrum corresponded to the structure of the desired product.

후처리

  1. customAfter completion of reaction the solution
  2. temperaturewas cooled
  3. washwashed with water (40 mL), diluted hydrochloric acid (40 ml), 5% aqueous sodium hydrogen carbonate (40 mL) and water (50 mL)
  4. dry with materialThe solution was dried over sodium sulfate
  5. customevaporated to dryness

출처 및 근거

ORD 기록
ord-c7dab20f920243519d7e00efb131103e
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829208B2

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