Water → N-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-phenyl)-N-methyl-carbamic Acid Tert-Butyl Ester

HRID 902634Notes

Reaction equation

HRID 902634 reaction equation
[C:1]([O:5][C:6](=[O:45])[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH2:15][CH2:16][CH2:17][N:18]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[C:35]=2[Cl:44])[CH2:19][CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:48]I.O>CN(C=O)C>[C:1]([O:5][C:6](=[O:45])[N:7]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH2:15][CH2:16][CH2:17][N:18]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:42])([F:43])[F:41])[C:35]=2[Cl:44])[CH2:19][CH:20]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:9]=1)[CH3:48])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10175511(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propoxy}-phenyl)-carbamic acid tert-butyl ester

Product 1

HCID 69252425N-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-phenyl)-N-methyl-carbamic Acid Tert-Butyl EsterYield 99.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

N-(3-{3-[(2-Chloro-3-trifluoromethyl-benzyl)-2,2-diphenylethyl-amino]-propoxy}-phenyl)-carbamic acid tert-butyl ester (1.05 g, 1.64 mmol) was dissolved in anhydrous DMF (10 mL) and cooled to 0° C. under argon. NaH (78.8 mg, 1.97 mmol, 60% dispersion in mineral oil) was added and the mixture stirred at 0° C. for 30 minutes. Methyl iodide (164 uL, 2.63 mmol) was added and the reaction was allowed to warm to room temperature at which point the solution was maintained for 18 hours. The reaction mixture was then poured into H2O and extracted twice with EtOAc. The combined EtOAc extracts were washed with saturated aqueous NaCl, dried over Na2SO4, filtered, and concentrated to a yellow oil which was further purified by silica gel chromatography (10 g Redisep column, silica, 40 um, 60 Å, 35 mL/min, A: hexanes, B: EtOAc, B: 0% for 5 min, B: 0% to 10% over 10 min; B: 10% for 10 min; B: 10% to 30% over 15 min; B: 30% for 10 min; detection at 214 nm) to give 1.05 g (1.63 mmol, 99%) of the title compound as a yellow oil. MS (ESI) 653.2

Workup

  1. temperatureto warm to room temperature at which point the solution
  2. temperaturewas maintained for 18 hours
  3. extractionextracted twice with EtOAc
  4. washThe combined EtOAc extracts were washed with saturated aqueous NaCl
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to a yellow oil which
  8. customwas further purified by silica gel chromatography (10 g Redisep column, silica, 40 um, 60 Å, 35 mL/min
  9. waitA: hexanes, B: EtOAc, B: 0% for 5 min
  10. waitB: 0% to 10% over 10 min
  11. waitB: 10% for 10 min
  12. waitB: 10% to 30% over 15 min
  13. waitB: 30% for 10 min

Sources & evidence

ORD record
ord-207f9e81c45641b0bc1b7f739cd9e217
Source dataset
uspto-grants-2008_04
Patent number
US07365085B2

Reaction notes

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