Acetic Acid → methyl(7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

HRID 498994Notes

Reaction equation

HRID 498994 reaction equation
O=[CH:2][CH2:3][NH:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[CH:12]1([C:18]2[C:19]3[CH:20]=[CH:21][C:22]([C:39]([O:41][CH3:42])=[O:40])=[CH:23][C:24]=3[N:25]3[C:32]=2[C:31]2[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=2[O:29][CH2:28][C@H:27]([NH:37][CH3:38])[CH2:26]3)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.C(O)(=O)C.C([O-])(=O)C.[Na+]>CO.[Pd]>[C:7]([O:6][C:5]([NH:4][CH2:3][CH2:2][N:37]([CH3:38])[C@@H:27]1[CH2:26][N:25]2[C:24]3[CH:23]=[C:22]([C:39]([O:41][CH3:42])=[O:40])[CH:21]=[CH:20][C:19]=3[C:18]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)=[C:32]2[C:31]2[CH:33]=[CH:34][CH:35]=[CH:36][C:30]=2[O:29][CH2:28]1)=[O:11])([CH3:10])([CH3:9])[CH3:8]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 517045Sodium AcetateHCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 66674181methyl(7R)-14-cyclohexyl-7-(methylamino)-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

Product 1

HCID 53381224methyl(7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylateYield 82%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent3×

Procedure

To a solution of tert-butyl (2-oxoethyl)carbamate (1 eq; 0.38 M) in dry methanol was added a mixture of methyl (7R)-14-cyclohexyl-7-(methylamino)-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (0.14 M), acetic acid (2 eq) and sodium acetate (1 eq) in dry methanol, and the mixture stirred at RT for 15 min. Then Pd/C (0.3 weight eq) was added as a slurry in MeOH under N2. The atmosphere in the reaction vessel was charged with H2 and the reaction stirred vigorously under a H2 atmosphere (balloon) at 60° C. overnight. The reaction was allowed to cool to RT, flushed with N2 and filtered through a plug of CELITE. The filtrate was concentrated in vacuo and the residue purified by FC (PE/EtOAc 2.5:1 to 1.5:1 gradient) to afford the title compound (82%). (ES+) m/z 562 (M+H)+; [α]D+67.1, c=0.67, CHCl3

Workup

  1. additionThe atmosphere in the reaction vessel was charged with H2
  2. stirringthe reaction stirred vigorously under a H2 atmosphere (balloon) at 60° C. overnight
  3. temperatureto cool to RT
  4. customflushed with N2
  5. filtrationfiltered through a plug of CELITE
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue purified by FC (PE/EtOAc 2.5:1 to 1.5:1 gradient)

Sources & evidence

ORD record
ord-5a68015eda0040fba78a6be6f79c1e76
Source dataset
uspto-grants-2010_08
Patent number
US07767660B2

Reaction notes

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