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

HRID 73815Notes

Reaction equation

HRID 73815 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-c7dab20f920243519d7e00efb131103e
Source dataset
uspto-grants-2014_09
Patent number
US08829208B2

Reaction notes

Loading…