Water → (S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-isopropyl ester 7-methyl ester

HRID 602883Notes

Reaction equation

HRID 602883 reaction equation
[CH3:1][O:2][C:3]([C@@H:5]1[CH2:14][C:13]2[C:8](=[CH:9][C:10]([OH:16])=[C:11]([NH2:15])[CH:12]=2)[CH2:7][N:6]1[C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18])=[O:4].O.C(=O)(O)[O-].[Na+].Cl[CH:30]([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH2:41][C:42]2[CH:47]=[CH:46][C:45]([Cl:48])=[C:44]([Cl:49])[CH:43]=2)=[CH:36][CH:35]=1)[C:31](Cl)=[O:32]>CCOC(C)=O>[CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]2[CH:12]=[C:11]3[C:10]([O:16][C@@H:30]([C:34]4[CH:39]=[CH:38][C:37]([O:40][CH2:41][C:42]5[CH:47]=[CH:46][C:45]([Cl:48])=[C:44]([Cl:49])[CH:43]=5)=[CH:36][CH:35]=4)[C:31](=[O:32])[NH:15]3)=[CH:9][C:8]=2[CH2:7][N:6]1[C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18])=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 593375102-Chloro-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-acetyl chlorideHCID 66923063(S)-6-amino-7-hydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-isopropyl ester 3-methyl ester

Product 1

HCID 66923079(S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-isopropyl ester 7-methyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

(S)-6-amino-7-hydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-isopropyl ester 3-methyl ester (1.8 g) was dissolved in 10 mL EtOAc, 20 mL water and 5.0 g sodium bicarbonate added. 2-Chloro-2-[4-(3,4-dichloro-benzyloxy)-phenyl]-acetyl chloride in 10 mL of EtOAc was added and the mixture stirred at rt for 1.5 h. The organic layer was washed with brine, dried and evaporated. The residue was dissolved in 15 mL DMF and potassium carbonate (4.1 g) added. The mixture stirred at rt for 3 h and was poured onto water and EtOAc. The organic was washed with 1N HCl, dried and evaporated. The residue was purified over silica (hexanes-EtOAc-2M ammonia in MeOH) to provide (S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2-oxo-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-isopropyl ester 7-methyl ester (2.0 g). LC-MS (m/z) 600.

Workup

  1. washThe organic layer was washed with brine
  2. customdried
  3. customevaporated
  4. dissolutionThe residue was dissolved in 15 mL DMF
  5. additionpotassium carbonate (4.1 g) added
  6. stirringThe mixture stirred at rt for 3 h
  7. additionwas poured onto water and EtOAc
  8. washThe organic was washed with 1N HCl
  9. customdried
  10. customevaporated
  11. customThe residue was purified over silica (hexanes-EtOAc-2M ammonia in MeOH)

Sources & evidence

ORD record
ord-683867cc80b84138b6ed3feea40f68e8
Source dataset
uspto-grants-2011_03
Patent number
US07906507B2

Reaction notes

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