Sodium hydride → Ammonium Hydroxide

HRID 1017044Notes

Reaction equation

HRID 1017044 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]([CH:12]=[CH:13][CH:14]=1)[NH2:11])C1C=CC=CC=1.[H-].[Na+].FC(F)(F)O[C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23]Br>C1CCCCC1>[OH-:1].[NH4+:11].[CH2:23]([NH:11][C:10]1[CH:9]=[CH:8][CH:14]=[CH:13][CH:12]=1)[C:22]1[CH:25]=[CH:26][CH:27]=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 771353-PhenoxyanilineHCID 7371761-(Bromomethyl)-3-(trifluoromethoxy)benzene2×

Product 2

HCID 14923Ammonium HydroxideHCID 66028Benzylaniline

Reagents, catalysts & solvents 1

HCID 8078CyclohexaneSolvent

Procedure

EX-1671A) To a solution of 3-phenoxyaniline (10.9 g, 58.8 mmol) in 100 mL of cyclohexane was added solid NaH (60% in mineral oil, 1.96 g, 49 mmol). Then 3-trifluoromethoxybenzyl bromide (10.0 g, 39.2 mmol) was added dropwise under a nitrogen atmosphere, and the mixture was heated to reflux for 18 h, at which time TLC analysis indicated that no 3-trifluoromethoxybenzyl bromide remained. The reaction mixture was cooled to room temperature and quenched with water, then extracted with ether. The ether layer was washed with water and brine, then dried over MgSO4, and evaporated to give crude product. The crude product was purified by flash column chromatography on silica gel eluting with 1:7:0.01 of ethyl acetatehexane:ammonium hydroxide to give the desired N-benzylaniline product, which contained a small portion of dibenzylated amine. This product was further purified by conversion to the corresponding HCl salt to give 11.0 g (73%) of the desired N-(3-phenoxyphenyl)-N-[(3-trifluoromethoxy)phenyl]methyl]amine hydrochloride product. HRMS calcd. for C20H16NO2F3: 360.1211 [M+H]+, found 360.1208.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 18 h, at which time TLC analysis
  3. customquenched with water
  4. extractionextracted with ether
  5. washThe ether layer was washed with water and brine
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customto give crude product
  9. customThe crude product was purified by flash column chromatography on silica gel eluting with 1:7:0.01 of ethyl acetatehexane

Sources & evidence

ORD record
ord-1dc548f078094ad08249a258cb347b5f
Source dataset
uspto-grants-2002_11
Patent number
US06476057B1

Reaction notes

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