Potassium bis(trimethylsilyl)amide → HCID 11584225, compound

HRID 1028513Notes

Reaction equation

HRID 1028513 reaction equation
[NH2:1][CH:2]([C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=1)[CH2:3][N:4]([CH2:15][C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[CH:18][C:17]=1[C:26]1[CH:31]=[C:30]([CH:32]([CH3:34])[CH3:33])[CH:29]=[CH:28][C:27]=1[O:35][CH3:36])[C:5](=[O:14])OCC1C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>C1COCC1.C1(C)C=CC=CC=1>[Cl:43][C:40]1[CH:41]=[CH:42][C:37]([CH:2]2[CH2:3][N:4]([CH2:15][C:16]3[CH:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=[CH:18][C:17]=3[C:26]3[CH:31]=[C:30]([CH:32]([CH3:33])[CH3:34])[CH:29]=[CH:28][C:27]=3[O:35][CH3:36])[C:5](=[O:14])[NH:1]2)=[CH:38][CH:39]=1

Participants

5

Reactant 2

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 66716659HCID 66716659, compound

Product 1

HCID 11584225HCID 11584225, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of benzyl [2-amino-2-(4-chlorophenyl)ethyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate (30 mg, 0.05 mmol) in THF (2 mL) was added potassium bis(trimethylsilyl)amide (295 μL of a 0.5M solution in toluene, 0.147 mmol) The reaction was stirred at room temperature for 30 minutes and then quenched with saturated NH4Cl (15 mL). The resultant mixture was extracted with EtOAc (25 mL) and the organic layer was washed with H2O (15 mL) and brine (15 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 5% to 60% EtOAc/hexanes afforded 4-(4-chlorophenyl)-1-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}imidazolidin-2-one. Rf=0.46 (5% MeOH/CH2Cl2). LCMS=503.1 (M+1)+. 1H NMR (C6D6, 600 MHz, atropisomers observed; doubling of peaks.) δ 7.90-7.03 (m, 6H), 6.89-6.20 (m, 4H), 4.69-3.88 (m, 3H), 3.16 (s, 3H), 2.88-2.30 (m, 3H), 1.18-1.13 (m, 6H).

Workup

  1. customquenched with saturated NH4Cl (15 mL)
  2. extractionThe resultant mixture was extracted with EtOAc (25 mL)
  3. washthe organic layer was washed with H2O (15 mL) and brine (15 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification of the residue by flash chromatography with 5% to 60% EtOAc/hexanes

Sources & evidence

ORD record
ord-860b17453da247d6871f6733184af9b0
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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