Benzyl chloroformate → (1S,9S)-tert-butyl 9-(benzyloxycarbonylamino)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate

HRID 1532892Notes

Reaction equation

HRID 1532892 reaction equation
Cl[C:2]([O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[O:3].[NH2:12][C@@H:13]1[C:19](=[O:20])[N:18]2[C@H:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22][CH2:23][CH2:24][N:17]2[C:16](=[O:32])[CH2:15][CH2:14]1.C([O-])(O)=O.[Na+].O1CCOCC1>CCOC(C)=O.O>[CH2:5]([O:4][C:2]([NH:12][C@@H:13]1[C:19](=[O:20])[N:18]2[C@H:21]([C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[CH2:22][CH2:23][CH2:24][N:17]2[C:16](=[O:32])[CH2:15][CH2:14]1)=[O:3])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

7

Reactant 4

HCID 10387Benzyl chloroformateHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 15434568tert-Butyl (1S,9S)-9-amino-6,10-dioxooctahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate

Product 1

HCID 67022104(1S,9S)-tert-butyl 9-(benzyloxycarbonylamino)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylateYield 88.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Benzyl chloroformate (1.07 g) was added dropwise to a stirred ice cold mixture of the (1S,9S) t-butyl 9-amino-6,10-dioxo-1,2,3,4,7,8,9,10-octahydro-6H-pyridazino[1,2-a][1,2]diazepine-1-carboxylate (GB 2,128,984; 1.55 g, 5.21 mmol), NaHCO3 (0.66 g, 7.82 mmol), dioxan (32 ml) and water (8 ml). The mixture was kept at 5° C. for 15 min then for 2 h at room temperature. The mixture was diluted with EtOAc (50 ml), washed twice with sat. NaHCO3 solution, dried (MgSO4) and concentrated. The oily residue was purified by flash chromatography to afford 211d (1.98 g, 88%) of a colourless oil: [α]D24 −56.4 (c 1.0, CH2Cl2); IR(thin film) 3325, 2979, 2946, 1728, 1677, 1528, 1456, 1422, 1370, 1340, 1272, 1245, 1156, 1122, 1056, 916, 734, 699; 1H NMR (CDCl3) δ 7.29 (5H, m), 5.81-5.72 (1H, m), 5.26-5.20 (1H, m), 5.05 (2H, s), 4.69-4.51 (2H, m), 3.48-3.36 (1H, m), 2.81-2.51 (2H, m), 2.34-2.19 (2H, m), 1.90-1.54 (4H, m), 1.41 (9H, s); Anal. Calcd for C22H29N3O6•H2O: C, 58.79; H, 6.92; N, 9.35. Found: C, 59.10; H, 6.57; N, 9.25; MS (ES +) 454 (M++Na, 87%), 432 (M++1, 100).

Workup

  1. waitfor 2 h at room temperature
  2. washwashed twice with sat. NaHCO3 solution
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe oily residue was purified by flash chromatography

Sources & evidence

ORD record
ord-410641a5bc724c34bef2ee2fc856687f
Source dataset
uspto-grants-2001_03
Patent number
US06204261B1

Reaction notes

Loading…