Methyl iodide → Methyl-{2-[4-(3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester

HRID 474718Notes

Reaction equation

HRID 474718 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:26])([F:25])[F:24])[CH:18]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:28]I>C1COCC1.[H-].[Na+]>[C:1]([O:5][C:6](=[O:27])[N:7]([CH3:28])[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]([F:25])([F:26])[F:24])[CH:18]=2)=[CH:12][CH:11]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 6328Methyl iodideHCID 67772730{2-[4-(3-Trifluoromethyl-phenoxy)-phenyl]ethyl}-carbamic acid tert-butyl ester

Product 1

HCID 67774263Methyl-{2-[4-(3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl esterYield 88.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 24758Sodium hydrideSolvent

Procedure

{2-[4-(3-Trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (333 mg, 0.873 mmol, 1 eq) was dissolved in dry THF (4.5 ml) and NaH, 60% (101 mg, 2.53 mmol, 2.9 eq) was added. After 30 min, the reaction mixture was treated with methyl iodide (545 μl, 8.73 mmol, 10 eq) and was stirred overnight. After overnight the excess NaH was quenched by a slow addition of water, diluted with brine (30 ml) and extracted with Et2O (3×20 ml). Combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated to give a product methyl-{2-[4-(3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (306 mg, yield=78%, purity=88%). [M+H]+=396.43 1H NMR (300 MHz; CDCl3) δ/ppm 1.43 (s, 9H), 2.74-2.93(m, 5H), 3.44 (t, J=8.53 Hz, 2H), 6.92-6.99 (m, 2H), 7.09-7.24 (m, 4H), 7.29-7.35 (m, 1H), 7.37-7.45 (m, 1H)

Workup

  1. customAfter overnight the excess NaH was quenched by a slow addition of water
  2. additiondiluted with brine (30 ml)
  3. extractionextracted with Et2O (3×20 ml)
  4. dry with materialCombined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-663cb16dcf4d47b8adb25a9c807463d0
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

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