3-Phenoxyaniline → N-(3-phenoxyphenyl)[[3-(2,2,2-trifluoroethoxy)phenyl]methyl]amine

HRID 1840055Notes

Reaction equation

[F:1][C:2]([F:14])([F:13])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH:8]=O.[O:15]([C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][CH:28]=1)[NH2:25])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[BH4-].[Na+]>C1CCCCC1>[O:15]([C:22]1[CH:23]=[C:24]([NH:25][CH2:8][C:7]2[CH:10]=[CH:11][CH:12]=[C:5]([O:4][CH2:3][C:2]([F:14])([F:13])[F:1])[CH:6]=2)[CH:26]=[CH:27][CH:28]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

Conditions

Temperature: 80 °C

Procedure

The 3-(2,2,2-trifluoroethoxy)benzaldehyde (0.360 g, 1.76 mmol) product from EX-659A and 3-phenoxyaniline (0.326 g, 1.76 mmol) were combined in 50 mL of cyclohexane with 3A molecular sieves (1 g) and stirred overnight at 80° C. The mixture was cooled, filtered, and evaporated, then dissolved in 50 mL of methanol and cooled to 0° C. Solid sodium borohydride (0.030 g, 0.79 mmol) was added in portions, and the mixture was stirred overnight. The reaction was quenched with 5% aq. NaHCO3 and extracted with ether (3×). The combined ether layers were washed with water and brine, dried over MgSO4, filtered, and evaporated to give 0.50 g (76%) of the desired N-(3-phenoxyphenyl)[[3-(2,2,2-trifluoroethoxy)phenyl]methyl]amine product as an amber oil, >95% pure by normal phase HPLC analysis. MS m/z=373 [M+].

Workup

temperatureThe mixture was cooled
filtrationfiltered
customevaporated
dissolutiondissolved in 50 mL of methanol
temperaturecooled to 0° C
stirringthe mixture was stirred overnight
customThe reaction was quenched with 5% aq. NaHCO3
extractionextracted with ether (3×)
washThe combined ether layers were washed with water and brine
dry with materialdried over MgSO4
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-d202c4c78e9e437591066a98eb06cf92
Source dataset: uspto-grants-2004_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06677375B2

Reaction notes

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