7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl 3-[2-(bis-benzyloxy-phosphoryloxy)-4,6-dimethyl-phenyl]-3-methyl-butyrate → 7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl 3-(2,4-dimethyl-6-phosphonooxy-phenyl)-3-methyl-butyrate

HRID 1519473Notes

Reaction equation

HRID 1519473 reaction equation
C([O:8][P:9]([O:58]CC1C=CC=CC=1)([O:11][C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[C:13]=1[C:20]([CH3:57])([CH3:56])[CH2:21][C:22]([O:24][CH:25]1[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:50])[C:33]2[CH:38]=[CH:37][C:36]([NH:39][C:40](=[O:48])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=3[CH3:47])=[CH:35][C:34]=2[CH3:49])[C:27]2[CH:51]=[CH:52][C:53]([Cl:55])=[CH:54][C:26]1=2)=[O:23])=[O:10])C1C=CC=CC=1>C(OCC)(=O)C.[C].[Pt]>[CH3:19][C:14]1[CH:15]=[C:16]([CH3:18])[CH:17]=[C:12]([O:11][P:9]([OH:58])([OH:10])=[O:8])[C:13]=1[C:20]([CH3:57])([CH3:56])[CH2:21][C:22]([O:24][CH:25]1[CH2:31][CH2:30][CH2:29][N:28]([C:32](=[O:50])[C:33]2[CH:38]=[CH:37][C:36]([NH:39][C:40](=[O:48])[C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=3[CH3:47])=[CH:35][C:34]=2[CH3:49])[C:27]2[CH:51]=[CH:52][C:53]([Cl:55])=[CH:54][C:26]1=2)=[O:23]

Participants

4

Reactant 1

HCID 251342137-chloro-1-[2-methyl-4-(2-methylbenzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl 3-[2-(bis-benzyloxy-phosphoryloxy)-4,6-dimethyl-phenyl]-3-methyl-butyrate

Product 1

HCID 468934167-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl 3-(2,4-dimethyl-6-phosphonooxy-phenyl)-3-methyl-butyrateYield 28.4%

Reagents, catalysts & solvents 2

HCID 178503042HCID 178503042, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl 3-[2-(bis-benzyloxy-phosphoryloxy)-4,6-dimethyl-phenyl]-3-methyl-butyrate (0.92 g) in ethyl acetate (10 ml) was hydrogenated over 5% platinum carbon (100 mg). The catalyst was removed by filtration through Celite layer, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (dichloromethane:methanol=90:10→50:50). The purified product was concentrated under reduced pressure, and the aqueous acetonitrile solution of the residue was freeze-dried to obtain 0.21 g of 7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl 3-(2,4-dimethyl-6-phosphonooxy-phenyl)-3-methyl-butyrate as white amorphous solid.

Workup

  1. customThe catalyst was removed by filtration through Celite layer
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by silica gel flash chromatography (dichloromethane:methanol=90:10→50:50)
  4. concentrationThe purified product was concentrated under reduced pressure
  5. dry with materialthe aqueous acetonitrile solution of the residue was freeze-dried

Sources & evidence

ORD record
ord-5f4320363e1c40b594ee979061ae16cd
Source dataset
uspto-grants-2015_07
Patent number
US09073868B2

Reaction notes

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