Water → [(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] N-[(7S)-5-[(4-methoxyphenyl)methyl]-6-oxo-7H-benzo[d][1]benzazepin-7-yl]carbamate

HRID 2105895Notes

Reaction equation

HRID 2105895 reaction equation
O.[NH2:2][CH:3]1[C:9](=[O:10])[N:8]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[C:7]2[CH:20]=[CH:21][CH:22]=[CH:23][C:6]=2[C:5]2[CH:24]=[CH:25][CH:26]=[CH:27][C:4]1=2.C([O-])([O-])=O.[K+].[K+].Cl[C:35]([O:37][CH:38]1[CH:43]([CH:44]([CH3:46])[CH3:45])[CH2:42][CH2:41][C@@H:40]([CH3:47])[CH2:39]1)=[O:36]>C1COCC1>[CH:44]([C@@H:43]1[CH2:42][CH2:41][C@@H:40]([CH3:47])[CH2:39][C@H:38]1[O:37][C:35](=[O:36])[NH:2][C@@H:3]1[C:9](=[O:10])[N:8]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)[C:7]2[CH:20]=[CH:21][CH:22]=[CH:23][C:6]=2[C:5]2[CH:24]=[CH:25][CH:26]=[CH:27][C:4]1=2)([CH3:45])[CH3:46]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 20577931(-)-(r)-Menthyl chloroformateHCID 210725617-Amino-5-(4-methoxybenzyl)-5,7-dihydro-6H-dibenzo[b,d]azepin-6-one

Product 1

HCID 44516082[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] N-[(7S)-5-[(4-methoxyphenyl)methyl]-6-oxo-7H-benzo[d][1]benzazepin-7-yl]carbamateYield 45%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Water (40 mL) was added to a yellow solution of 7-amino-5-(4-methoxy-benzyl)-5H,7H-dibenzo[b,d]azepin-6-one (7.45 g) in THF (40 mL) at room temperature forming a light yellow suspension. To this suspension were added K2CO3 (5.53 g) in one portion and, after 15 minutes of stirring, (−)-(1R)-menthyl chloroformate (4.96 g) was added within 30 minutes. The dropping funnel was washed with THF. The emulsion was stirred for 105 minutes at room temperature. Heptane (486 mL) was added within 40 minutes and, after 60 more minutes of stirring, the precipitate was filtered off, washed with heptane, water, and then heptane in that order and dried under vacuum at 55° C. to afford [(S)-5-(4-methoxy-benzyl)-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-carbamic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester (4.75 g, 45%), d.e=99.8:0.2 (HPLC), as a white powder.

Workup

  1. customforming a light yellow suspension
  2. washThe dropping funnel was washed with THF
  3. stirringThe emulsion was stirred for 105 minutes at room temperature
  4. additionHeptane (486 mL) was added within 40 minutes
  5. stirringafter 60 more minutes of stirring
  6. filtrationthe precipitate was filtered off
  7. washwashed with heptane, water
  8. dry with materialheptane in that order and dried under vacuum at 55° C.

Sources & evidence

ORD record
ord-269b16f100d84dc3b02fc1a91f3a7d1a
Source dataset
uspto-grants-2009_08
Patent number
US07579464B2

Reaction notes

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