1-[(2-bromoethoxy)methyl]-4-methoxybenzene → HCID 67311654, compound

HRID 2192361Notes

Reaction equation

HRID 2192361 reaction equation
Br[CH2:2][CH2:3][O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[CH:8][CH:7]=1.[N:14]12[CH2:21][CH2:20][CH:17]([CH2:18][CH2:19]1)[C@@H:16]([O:22][C:23]([C:25]1([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)=[O:24])[CH2:15]2>CC#N>[CH:23]([O-:24])=[O:22].[CH3:13][O:12][C:9]1[CH:10]=[CH:11][C:6]([CH2:5][O:4][CH2:3][CH2:2][N+:14]23[CH2:21][CH2:20][CH:17]([CH2:18][CH2:19]2)[C@@H:16]([O:22][C:23]([C:25]2([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)=[O:24])[CH2:15]3)=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 117015101-[(2-bromoethoxy)methyl]-4-methoxybenzene2×HCID 591796191-Phenyl-cycloheptanecarboxylic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

Product 1

HCID 67311654HCID 67311654, compoundYield 148.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 1-(2-bromo-ethoxymethyl)-4-methoxy-benzene (42 mg) and 1-phenyl-cycloheptanecarboxylic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester (Example 14e) (50 mg) in MeCN (1 mL) was stirred at room temperature for 16 h then heated to 80° C. under nitrogen overnight. A further 1.1 equivalents of 1-(2-bromo-ethoxymethyl)-4-methoxy -benzene were added and the mixture was heated at 80° C. for a further 48 h. The volatiles were evaporated and the crude product was purified by silica gel chromatography eluting with 0-10% of a 10% conc. NH3/MeOH solution in dichloromethane give 61 mg of an oil that was purified further by reverse phase HPLC (Gemini 5 μM C6 phenyl column) eluting with 5-95% MeOH/H2O containing 0.1% formic acid over 30 min with UV detection at 220 nm. The relevant fractions were combined and evaporated to afford the title compound (34 mg) as an oil.

Workup

  1. temperaturethen heated to 80° C. under nitrogen overnight
  2. temperaturethe mixture was heated at 80° C. for a further 48 h
  3. customThe volatiles were evaporated
  4. customthe crude product was purified by silica gel chromatography
  5. washeluting with 0-10% of a 10% conc. NH3/MeOH solution in dichloromethane

Sources & evidence

ORD record
ord-00ca82777f5e4b7890fe7f4147cac5ab
Source dataset
uspto-grants-2012_12
Patent number
US08329729B2

Reaction notes

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