Sodium Carbonate → (3S,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

HRID 1427962Notes

Reaction equation

HRID 1427962 reaction equation
[CH:1]([C@@H:4]1[CH2:9][CH2:8][C@@H:7]([CH3:10])[CH2:6][C@H:5]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][CH2:37][C:38]5[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=5)=[CH:32][CH:31]=4)[C:22](=[O:29])[N:23]3[CH3:28])=[CH:18][C:17]=2[CH2:16][NH:15]1)=[O:13])([CH3:3])[CH3:2].C(=O)(O)[O-].[Na+].Br[CH:52]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[CH2:53][CH3:54].C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C>[CH:1]([C@@H:4]1[CH2:9][CH2:8][C@@H:7]([CH3:10])[CH2:6][C@H:5]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:31]=[CH:32][C:33]([O:36][CH2:37][C:38]5[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([Cl:45])[CH:39]=5)=[CH:34][CH:35]=4)[C:22](=[O:29])[N:23]3[CH3:28])=[CH:18][C:17]=2[CH2:16][N:15]1[C@H:52]([C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)[CH2:53][CH3:54])=[O:13])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 562384(1-Bromopropyl)benzeneHCID 59337453(3S,7S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-1-methyl-2-oxo-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 59337422(3S,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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

(3S,7S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-1-methyl-2-oxo-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 (3.5 g, 5.37 mmol) was dissolved in 10 mL DMF and sodium bicarbonate (21.5 mmol) and (1-Bromo-propyl)-benzene (10.7 mmol) added. The mixture was stirred at 50° C. for 20 h and room temperature for 48 hours. The mixture was poured onto diethyl ether and 10% sodium carbonate. The aqueous layer was extracted with ether and organic layers combined. The organic layer was dried over sodium sulfate and concentrated. The residue was purified over silica (EtOAc-hexanes-DCM-TEA, 0.5/5/4.5/0.02) to provide (3S,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 (803 mg, 1H NMR (400 MHz, d6 acetone): 7.7 (d, 1H), 7.6 (d, 1H), 7.46 (d, 1H), 7.33 (m, 7H), 6.98 (m, 2H), 6.87 (s, 1H), 6.77 (s, 1H), 5.65 (s, 1H), 5.13 (s, 2H), 4.55 (m, 1H), 4.20 (s, 2H), 3.9 (m, 1H), 3.55 (m, 1H), 3.38 (s, 3H), 2.95 (m, 2H), 1.6 (m, 6H), 1.15 (m, 1H), 0.95 (m, 1H) 0.9 (m, 2H), 0.8 (m, 4H), 0.7 (d, 3H), 0.65 (m, 6H).

Workup

  1. extractionThe aqueous layer was extracted with ether and organic layers
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified over silica (EtOAc-hexanes-DCM-TEA, 0.5/5/4.5/0.02)

Sources & evidence

ORD record
ord-758575368e0d4cc7a145c1ef9a16ba17
Source dataset
uspto-grants-2015_01
Patent number
US08933222B2

Reaction notes

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