Acetonitrile → 3-[(3-Phenoxyphenyl)[[3-(tetrahydro-2-furanyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 1017011Notes

Reaction equation

HRID 1017011 reaction equation
CC#N.[O:4]([C:11]1[CH:12]=[C:13]([NH:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]3[CH2:29][CH2:28][CH2:27][O:26]3)[CH:20]=2)[CH:14]=[CH:15][CH:16]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[F:30][C:31]([F:36])([F:35])[CH:32]1[O:34][CH2:33]1.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.C(S([O-])(=O)=O)(F)(F)F.[Yb+3]>C(OCC)C.CCO>[O:4]([C:11]1[CH:12]=[C:13]([N:17]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]3[CH2:29][CH2:28][CH2:27][O:26]3)[CH:20]=2)[CH2:33][CH:32]([OH:34])[C:31]([F:36])([F:35])[F:30])[CH:14]=[CH:15][CH:16]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 5207692-(Trifluoromethyl)oxiraneHCID 2733225Ytterbium triflateHCID 23506095N-(3-phenoxyphenyl)-[[3-(tetrahydro-2-furanyl)phenyl]methyl]amine

Product 1

HCID 235060483-[(3-Phenoxyphenyl)[[3-(tetrahydro-2-furanyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanolYield 30.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
40 °C

Procedure

To a CH3CN (1 mL) solution of the amine (0.32 g, 0.93 mmol) from EX-608E was added 1.1,1-trifluoro-2,3-epoxypropane (0.24 mL, 2.8 mmol) and Yb(OTf)3 (0.115 g, 0.18 mmol). The cloudy solution was stirred in a sealed flask at 40° C. for 18 h. The cooled reaction mixture was diluted with diethyl ether and washed with water and brine. The organic layer was dried (MgSO4) and evaporated to an oil. Purification by flash chromatography on silica gel eluting with 15% ethyl acetate in hexane gave an oil which was dissolved in EtOH, stripped and dried in vacuo to give 0.13 g (30%) of the desired 3-[(3-phenoxyphenyl)[[3-(tetrahydro-2-furanyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a colorless oil. Anal. calcd. for C26H26NO3F3.0.5 EtOH: C, 67.33; H, 6.04; N, 2.94.Found: C, 67.49; H, 6.08; N, 2.91.HRMS calcd. 458.1943 [M+H]+, found: 458.1937. 1H NMR (C6D6) δ0.45 (d, 1H), 1.43 (m, 3H), 1.79 (m, 1H), 1.99 (m, 1H), 3.24 (m, 1H), 3.43 (m, 1H), 3.76 (m, 2H), 4.24 (s, 2H), 4.60 (t, 1H), 6.35 (m, 1H), 6.43 (dd, 1H), 6.54 (dd, 1H), 6.8 (m, 2H), 6.9-7.0 (m, 7H), 7.15 (d, 1H).

Workup

  1. customThe cooled reaction mixture
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customevaporated to an oil
  5. customPurification by flash chromatography on silica gel eluting with 15% ethyl acetate in hexane
  6. customgave an oil which
  7. customdried in vacuo

Sources & evidence

ORD record
ord-b4d36698358743ca953e7c51998adf04
Source dataset
uspto-grants-2002_11
Patent number
US06476057B1

Reaction notes

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