Acetic Anhydride → tert-Butyl 3(R)-[(1S,2S)-2-(Acetylamino)-3-(3,5-difluorophenyl)-1-hydroxypropyl]-5-bromo-8-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1436737Notes

Reaction equation

HRID 1436737 reaction equation
[NH2:1][C@@H:2]([CH2:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[CH:27]=1)[C@@H:3]([C@H:5]1[CH2:14][C:13]2[C:8](=[C:9]([O:16][CH3:17])[CH:10]=[CH:11][C:12]=2[Br:15])[CH2:7][N:6]1[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[OH:4].C(N(CC)CC)C.[C:41](OC(=O)C)(=[O:43])[CH3:42]>O1CCCC1>[C:41]([NH:1][C@@H:2]([CH2:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[C:28]([F:33])[CH:27]=1)[C@@H:3]([C@H:5]1[CH2:14][C:13]2[C:8](=[C:9]([O:16][CH3:17])[CH:10]=[CH:11][C:12]=2[Br:15])[CH2:7][N:6]1[C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[OH:4])(=[O:43])[CH3:42]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 57938829tert-butyl (3R)-3-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxy-propyl]-5-bromo-8-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 69014743tert-Butyl 3(R)-[(1S,2S)-2-(Acetylamino)-3-(3,5-difluorophenyl)-1-hydroxypropyl]-5-bromo-8-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Slurry tert-butyl (3R)-3-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxy-propyl]-5-bromo-8-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (59.4 mg, 0.000113 mol) in tetrahydrofuran (1.00 mL). Add triethylamine (15.7 uL, 0.000113 mol) and acetic anhydride (10.6 uL, 0.000113 mol) and stir for 45 minutes. Dilute dichloro-methane (25 mL) and wash with water (1×10 mL), 0.1N HCl (1×10 mL), saturated aqueous sodium bicarbonate (1×10 mL), saturated aqueous sodium chloride (1×10 mL) and dry over magnesium sulfate. Concentrate the filtrate to give the desired product (57.9, 88%) as a white solid.

Workup

  1. washDilute dichloro-methane (25 mL) and wash with water (1×10 mL), 0.1N HCl (1×10 mL), saturated aqueous sodium bicarbonate (1×10 mL), saturated aqueous sodium chloride (1×10 mL)
  2. dry with materialdry over magnesium sulfate
  3. concentrationConcentrate the filtrate

Sources & evidence

ORD record
ord-3096993512a44869bde7faa7b6b0a90d
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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