Diethyl Pyrocarbonate → tert-butyl (1R,2S)-2-{[(3aR,4R,9bR)-4-phenyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexylcarbamate

HRID 550259

Reaction equation

HRID 550259 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]1[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])C.CCOC(OC(O[CH2:34][CH3:35])=O)=O.C(=O)([O-])O.[Na+].[CH3:41][N:42]([CH:44]=O)C>>[C:9]1([C@H:41]2[C@H:22]3[CH2:24][CH2:23][N:20]([C:15]([C@H:10]4[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]4[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:17])[C@H:21]3[C:35]3[CH:34]=[CH:3][CH:1]=[CH:2][C:44]=3[NH:42]2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 5

HCID 3051Diethyl PyrocarbonateHCID 6228Dimethylformamide2×HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 1512489(1S,2R)-2-(((tert-butoxy)carbonyl)amino)cyclohexane-1-carboxylic acid

Product 1

HCID 57846948tert-butyl (1R,2S)-2-{[(3aR,4R,9bR)-4-phenyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexylcarbamateYield 50%

Procedure

To a solution of the compound (13 g, 40.2 mmol) synthesized in Reference Example 8 and (1S,2R)-2-[(tert-butoxycarbonyl)amino]cyclohexanecarboxylic acid (11.7 g, 48.2 mmol) in DMF (200 ml) were added dropwise triethylamine (16.9 ml, 121 mmol) at 0° C. and subsequently a solution of DEPC (6.74 ml, 40.2 mmol) in DMF (40 ml). The mixture was stirred at the same temperature for 30 min., saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted twice with ethyl acetate. The extract was washed with saturated brine and dried (over anhydrous MgSO4). After concentration under reduced pressure, the obtained residue was subjected to column chromatography using silica gel, and eluted with hexane-ethyl acetate (10:1-1:1, v/v). tert-Butyl (1R,2S)-2-{[(3aR,4R,9bR)-4-phenyl-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexylcarbamate (9.57 g, 50%) was obtained as a colorless amorphous form from the first object eluted fraction.

Workup

  1. extractionthe mixture was extracted twice with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried (over anhydrous MgSO4)
  4. concentrationAfter concentration under reduced pressure
  5. washeluted with hexane-ethyl acetate (10:1-1:1

Sources & evidence

ORD record
ord-d7e1fb2726e04cf78bb5a9c55199bf5a
Source dataset
uspto-grants-2011_05
Patent number
US07943770B2

Linked notes

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