1,8-Diazabicyclo(5.4.0)undec-7-ene → (S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-3-hydroxy-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester 8-methyl ester

HRID 391772Notes

Reaction equation

HRID 391772 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]([OH:15])[CH:12]=2)[CH2:7][N:6]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:4].Br[CH2:25][C:26]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([Cl:43])[CH:37]=2)=[CH:30][CH:29]=1)=[O:27].C(=O)(O)[O-].[Na+].C1CCN2C(=NCCC2)CC1>CN(C=O)C.O.CCOC(C)=O>[CH3:1][O:2][C:3]([CH:5]1[CH2:14][C:13]2[CH:12]=[C:11]3[O:15][CH2:25][C@@:26]([C:28]4[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]5[CH:41]=[CH:40][C:39]([Cl:42])=[C:38]([Cl:43])[CH:37]=5)=[CH:30][CH:29]=4)([OH:27])[O:16][C:10]3=[CH:9][C:8]=2[CH2:7][N:6]1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])=[O:4]

Participants

8

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516892Sodium BicarbonateHCID 58327303(S)-6,7-dihydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl esterHCID 583275742-Bromo-1-[4-(3,4-dichloro-benzyloxy)-phenyl]-ethanone

Product 1

HCID 66719236(S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-3-hydroxy-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester 8-methyl esterYield 101.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-6,7-Dihydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester (30.0 g), 2-bromo-1-[4-(3,4-dichloro-benzyloxy)-phenyl]-ethanone (34.7 g), and sodium bicarbonate (7.8 g) were stirred together in 600 mL anhydrous DMF. While stirring at rt, DBU (6.95 mL) was added all at once and the mixture was stirred at rt for 18 hours. The reaction mixture was then poured into 1 L EtOAc and 500 mL water and the layers were separated. The organic layer was washed with water three times and brine once, then dried over sodium sulfate and concentrated to provide 57.8 g of orange foam which was used in the next step without further purification.

Workup

  1. stirringwas stirred at rt for 18 hours
  2. customthe layers were separated
  3. washThe organic layer was washed with water three times and brine once
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-9023d114c9db40d089af7592a10a1b2f
Source dataset
uspto-grants-2013_02
Patent number
US08383644B2

Reaction notes

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