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

HRID 879754Notes

Reaction equation

HRID 879754 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][C:19]=1[Cl:20])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:16])[CH:14]=O)=[CH:9][CH:8]=1.[CH3:21][O:22][C:23]([C@@H:25]1[CH2:34][C:33]2[C:28](=[CH:29][C:30](O)=[C:31]([NH2:35])[CH:32]=2)[CH2:27][N:26]1[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:24].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(Cl)Cl>ClCCCl.O>[CH3:21][O:22][C:23]([CH:25]1[CH2:34][C:33]2[CH:32]=[C:31]3[C:30]([O:16][C@@H:13]([C:10]4[CH:9]=[CH:8][C:7]([O:6][CH2:5][C:4]5[CH:17]=[CH:18][C:19]([Cl:20])=[C:2]([Cl:1])[CH:3]=5)=[CH:12][CH:11]=4)[CH2:14][NH:35]3)=[CH:29][C:28]=2[CH2:27][N:26]1[C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[O:24]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydrideHCID 59337426(S)-6-amino-7-hydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl esterHCID 86654900[4-(3,4-Dichloro-benzyloxy)-phenyl]-oxo-acetaldehyde

Product 1

HCID 66719396(S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-tert-butyl ester 7-methyl esterYield 71.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

[4-(3,4-Dichloro-benzyloxy)-phenyl]-oxo-acetaldehyde (616 mg) was dissolved in DCE (25 mL), and (S)-6-amino-7-hydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester (644 mg) and sodium triacetoxyborohydride (520 mg) were added. The mixture was stirred overnight at room temperature. DCM (50 mL) was added to the reaction mixture and poured into water (25 mL). The organic layer was washed with 10% Na2CO3 solution and brine, and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash chromatography (hexanes/ethyl acetate from 90:10 to 70:30) to give (S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-1,2,3,5,7,8-hexahydro-4-oxa-1,6-diaza-anthracene-6,7-dicarboxylic acid 6-tert-butyl ester 7-methyl ester (855 mg).

Workup

  1. washThe organic layer was washed with 10% Na2CO3 solution and brine
  2. dry with materialdried over sodium sulfate
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by flash chromatography (hexanes/ethyl acetate from 90:10 to 70:30)

Sources & evidence

ORD record
ord-708098122d724e3295f138eb574528d0
Source dataset
uspto-grants-2015_03
Patent number
US08987295B2

Reaction notes

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