Tetrahydrofuran → 3-[(3-Phenoxyphenyl)[[3-(phenylmethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 2122132Notes

Reaction equation

HRID 2122132 reaction equation
C1COCC1.[O:6]([C:13]1[CH:14]=[C:15]([N:19]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30](Br)[CH:29]=2)[CH2:20][CH:21]([OH:26])[C:22]([F:25])([F:24])[F:23])[CH:16]=[CH:17][CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:35]([Mg]Br)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.[NH4+].[Cl-]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[O:6]([C:13]1[CH:14]=[C:15]([N:19]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[CH:29]=2)[CH2:20][CH:21]([OH:26])[C:22]([F:25])([F:24])[F:23])[CH:16]=[CH:17][CH:18]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 25517Ammonium ChlorideHCID 110596773-[(3-Phenoxyphenyl)[[3-bromophenyl]methyl]amino]-1,1,1-trifluoro-2-propanolHCID 178419663HCID 178419663, compound

Product 1

HCID 235060073-[(3-Phenoxyphenyl)[[3-(phenylmethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanolYield 62%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 178418397HCID 178418397, compoundSolvent

Procedure

To a THF (4 mL) solution of 3-[(3-phenoxyphenyl)[[3-bromophenyl]methyl]amino]-1,1,1-trifluoro-2-propanol (0.60 g, 1.3 mmol) from EX-595B was added benzyl-magnesium bromide in THF (2.0 mL, 2.0 M, 4.0 mmol) and Pd(PPh3)4. The resulting yellow solution was refluxed under N2 for 18 h. The cooled solution was poured into saturated aq. NH4Cl, extracted with ethyl acetate, 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 0.39 g (62%) of the desired 3-[(3-phenoxyphenyl)[[3-(phenylmethyl)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a colorless oil. Anal. calcd. for C29H26NO2F3.0.4 EtOH: C, 72.17; H, 5.77; N, 2.82. Found: C, 72.17; H, 5.42; N, 2.83. HRMS calcd. 478.1994 ([M+H]+, found: 478.1984. 1H NMR (C6D6) δ 1.58 (d, 1H), 3.22 (dd, 1H), 3.46 (dd, 1H), 3.69 (s, 2H), 3.73 (m, 1H), 4.18 (s, 2H), 6.34 (dd, 1H), 6.47 (dd, 1H), 6.53 (t, 1H), 6.8-7.1 (m 15H).

Workup

  1. temperatureThe resulting yellow solution was refluxed under N2 for 18 h
  2. extractionextracted with ethyl acetate
  3. dry with materialdried (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-39542c00ff2343428ee0d4cf3b5a90e4
Source dataset
uspto-grants-2004_02
Patent number
US06696435B2

Reaction notes

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