Water → HCID 11648697, compound

HRID 1028514Notes

Reaction equation

HRID 1028514 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:33][CH3:34])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=2[CH2:20][N:21]2[CH2:25][C@@H:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[NH:23][C:22]2=[O:32])[CH:9]=1)([CH3:3])[CH3:2].CI.[CH3:37][Si]([N-][Si](C)(C)C)(C)C.[K+].O>C1COCC1.C1(C)C=CC=CC=1>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:33][CH3:34])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:12][C:11]=2[CH2:20][N:21]2[CH2:25][C@@H:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:23]([CH3:37])[C:22]2=[O:32])[CH:9]=1)([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 11626906HCID 11626906, compound

Product 1

HCID 11648697HCID 11648697, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (4R)-1-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-phenylimidazolidin-2-one (12.6 mg, 0.0269 mmol) in THF (1.5 mL) was added MeI (10 μL, 0.162 mmol), followed by KHMDS (162 μL of a 0.5 M solution in toluene, 0.081 mmol). The reaction was stirred at room temperature for 10 minutes, and then poured into water (10 mL). The mixture was extracted with EtOAc (30 mL) and the organic layer was washed with brine (10 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 50% EtOAc/hexanes afforded (4R)-1-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-3-methyl-4-phenylimidazolidin-2-one. Rf=0.26 (40% EtOAc/hexanes). LCMS=483.2 (M+1)+. 1H NMR (CDCl3, 500 MHz, atropisomers observed; doubling of peaks.) δ 7.68-7.53 (m, 2H), 7.21-7.36 (m, 7H), 6.87-6.94 (m, 2H), 4.08-4.56 (m, 3H), 3.72 & 3.71 (2 singlets, 3H), 3.34-3.38 (m, 1H), 2.77-2.89 (m, 2H), 2.67 & 2.63 (2 singlets, 3H), 1.18-1.26 (m, 6H).

Workup

  1. extractionThe mixture was extracted with EtOAc (30 mL)
  2. washthe organic layer was washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography with 50% EtOAc/hexanes

Sources & evidence

ORD record
ord-f51ebcb2028b40198dba13b538312898
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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