Hydrogen Bromide → 7-((2S,3'S)-2-Methyl-1,3'-bipyrrolidinyl-1'-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine

HRID 467577Notes

Reaction equation

HRID 467577 reaction equation
Br.COC([N:6]1[CH2:12][CH2:11][C:10]2[CH:13]=[C:14]([N:17]3[CH2:21][CH2:20][C@H:19]([N:22]4[CH2:26][CH2:25][CH2:24][C@@H:23]4[CH3:27])[CH2:18]3)[CH:15]=[CH:16][C:9]=2[CH2:8][CH2:7]1)=O>C(O)(=O)C>[CH3:27][C@H:23]1[CH2:24][CH2:25][CH2:26][N:22]1[C@H:19]1[CH2:20][CH2:21][N:17]([C:14]2[CH:15]=[CH:16][C:9]3[CH2:8][CH2:7][NH:6][CH2:12][CH2:11][C:10]=3[CH:13]=2)[CH2:18]1

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 682110197-((2S,3'S)-2-Methyl-[1,3']bipyrrolidinyl-1'-yl)-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid methyl ester

Product 1

HCID 546701937-((2S,3'S)-2-Methyl-1,3'-bipyrrolidinyl-1'-yl)-2,3,4,5-tetrahydro-1H-3-benzazepineYield 99.5%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Hydrobromic acid in acetic acid (28.4 mL of 33% by weight) was added to 7-((2S,3′S)-2-Methyl-[1,3′]bipyrrolidinyl-1′-yl)-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid methyl ester (700 mg, 1.96 mmol) and the mixture was stirred at ambient temperature for 24 h. The volatiles were removed in vacuo, and the residue was basified with saturated sodium bicarbonate solution and extracted into ethyl acetate (3×). The combined organic layers were washed with brine, dried over Magnesium sulfate, filtered and concentrated to leave 584 mg of an oil. This material was purified by column chromatography on silica gel (24 g SiO2, Analogix column) eluting @ 30 mL/min as follows: dichloromethane (containing 2% triethylamine for 5 min. then stepped to 85/15 dichloromethane (containing 2% triethylamine)/methanol in a linear gradient over 10 min to obtain 473 mg of the title compound as an oil.

Workup

  1. customThe volatiles were removed in vacuo
  2. extractionextracted into ethyl acetate (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-7a7adf35b4f344ad8395c2c7288612fe
Source dataset
uspto-grants-2014_01
Patent number
US08623877B2

Reaction notes

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