Acetic Acid → 6-Benzylamino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 1968901Notes

Reaction equation

HRID 1968901 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([NH2:18])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:19](=O)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 27563716-Amino-2-N-Boc-1,2,3,4-tetrahydro-isoquinolineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 672228296-Benzylamino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterYield 67.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 6-amino-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (350 mg, 1.41 mmol) in dichloromethane (15 ml) was added benzaldehyde (143 μl, 1.41 mmol), acetic acid (81 μl, 1.41 mmol) followed by sodium triacetoxyborohydride (418 mg, 1.97 mmol) and the reaction was stirred at room temperature for 16 hrs. The reaction mixture was quenched by cooling in ice batch and neutralising with aqueous sodium hydroxide 2M. The aqueous mixture was extracted using dichloromethane (3×50 ml) and the organics were combined, dried over sodium sulfate and then concentrated in vacuo. The crude residue was purified by column chromatography (1% methanol in dichloromethane) to afford the title compound as cream solid (320 mg, 67% yield). HPLC retention time 4.98 min. Mass spectrum (ES+) m/z 339 (M+H).

Workup

  1. customThe reaction mixture was quenched
  2. temperatureby cooling in ice batch
  3. extractionThe aqueous mixture was extracted
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by column chromatography (1% methanol in dichloromethane)

Sources & evidence

ORD record
ord-e0dbc7b25a9247669bedf02bc5e7a49f
Source dataset
uspto-grants-2013_04
Patent number
US08426442B2

Reaction notes

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