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 708654Notes

Reaction equation

HRID 708654 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.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:35][O:36][C:37]([C@@H:39]1[CH2:48][C:47]2[C:42](=[CH:43][C:44](O)=[C:45]([NH2:49])[CH:46]=2)[CH2:41][N:40]1[C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[O:38].C(Cl)Cl>ClCCCl.O>[CH3:35][O:36][C:37]([CH:39]1[CH2:48][C:47]2[CH:46]=[C:45]3[C:44]([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:49]3)=[CH:43][C:42]=2[CH2:41][N:40]1[C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])=[O:38]

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 sodium triacetoxyborohydride (520 mg) and (S)-6-Amino-7-hydroxy-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester 3-methyl ester (644 mg) 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 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 purified by flash chromatography (hexanes/ethyl acetate from 90:10 to 70:30)

Sources & evidence

ORD record
ord-c5f334ea7aa7449289c546b595452a11
Source dataset
uspto-grants-2015_11
Patent number
US09175003B2

Reaction notes

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