Boron Trichloride → (3R,7S)-3-(4-hydroxy-phenyl)-1-methyl-2-oxo-6-((S)-1-phenyl-propyl)-2,3,5,6,7,8-hexahydro-1H-4-oxa-1,6-diaza-anthracene-7-carboxylic acid

HRID 2369127Notes

Reaction equation

HRID 2369127 reaction equation
C([C@@H]1CC[C@@H](C)C[C@H]1[O:11][C:12]([C@@H:14]1[CH2:27][C:26]2[CH:25]=[C:24]3[C:19]([O:20][C@H:21]([C:30]4[CH:35]=[CH:34][C:33]([O:36]CC5C=CC(Cl)=C(Cl)C=5)=[CH:32][CH:31]=4)[C:22](=[O:29])[N:23]3[CH3:28])=[CH:18][C:17]=2[CH2:16][N:15]1[C@H:46]([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)[CH2:47][CH3:48])=[O:13])(C)C.B(Cl)(Cl)Cl>C(Cl)Cl.CCCCCC>[OH:36][C:33]1[CH:34]=[CH:35][C:30]([C@H:21]2[O:20][C:19]3[C:24](=[CH:25][C:26]4[CH2:27][C@@H:14]([C:12]([OH:13])=[O:11])[N:15]([C@H:46]([C:49]5[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=5)[CH2:47][CH3:48])[CH2:16][C:17]=4[CH:18]=3)[N:23]([CH3:28])[C:22]2=[O:29])=[CH:31][CH:32]=1

Participants

5

Reactant 2

HCID 25135Boron TrichlorideHCID 59337469(3R,7S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1-methyl-2-oxo-6-((S)-1-phenyl-propyl)-2,3,5,6,7,8-hexahydro-1H-4-oxa-1,6-diaza-anthracene-7-carboxylic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester

Product 1

HCID 59337507(3R,7S)-3-(4-hydroxy-phenyl)-1-methyl-2-oxo-6-((S)-1-phenyl-propyl)-2,3,5,6,7,8-hexahydro-1H-4-oxa-1,6-diaza-anthracene-7-carboxylic acidYield 129.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

To a solution of (3R,7S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-1-methyl-2-oxo-6-((S)-1-phenyl-propyl)-2,3,5,6,7,8-hexahydro-1H-4-oxa-1,6-diaza-anthracene-7-carboxylic acid (1R,2S,5R)-2-isopropyl-5-methyl-cyclohexyl ester (0.2 mmol) in DCM (3 mL) was added 1N BCl3 solution in hexane (0.5 mL) at 0° C. and the mixture was stirred for 3 h. The mixture was evaporated to dryness and the residue was quenched with water. The mixture was basified using sodium bicarbonate solution to pH 7. The residue was extracted with EtOAc and 10% THF. The organic layer was washed and dried to get (3R,7S)-3-(4-hydroxy-phenyl)-1-methyl-2-oxo-6-((S)-1-phenyl-propyl)-2,3,5,6,7,8-hexahydro-1H-4-oxa-1,6-diaza-anthracene-7-carboxylic acid as a yellow solid (122 mg). This solid was used as is for the next step.

Workup

  1. customThe mixture was evaporated to dryness
  2. customthe residue was quenched with water
  3. extractionThe residue was extracted with EtOAc and 10% THF
  4. washThe organic layer was washed
  5. customdried

Sources & evidence

ORD record
ord-09408d84557a49fd85173dfc8354f3ff
Source dataset
uspto-grants-2014_04
Patent number
US08703766B2

Reaction notes

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