Dimethyl Sulfate → HCID 57545984, compound

HRID 913890Notes

Reaction equation

HRID 913890 reaction equation
S(OC)(O[CH3:5])(=O)=O.[C:8]1([C:14]2([CH2:27][O:28][CH2:29][C:30]3[CH:31]=[C:32]([C:39]([F:42])([F:41])[F:40])[CH:33]=[C:34]4[C:38]=3[NH:37][CH:36]=[CH:35]4)[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CC(C)([O-])C.[K+]>O1CCCC1>[CH3:5][N:37]1[C:38]2[C:34](=[CH:33][C:32]([C:39]([F:41])([F:42])[F:40])=[CH:31][C:30]=2[CH2:29][O:28][CH2:27][C:14]2([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[CH2:18][CH2:19]2)[CH:35]=[CH:36]1

Participants

5

Reactant 3

HCID 6497Dimethyl SulfateHCID 23665647Potassium tert-butoxideHCID 57545939HCID 57545939, compound

Product 1

HCID 57545984HCID 57545984, compoundYield 65.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Dimethyl sulfate (0.020 ml, 0.209 mmol) was added to a solution of tert-butyl 4-phenyl-4-(((5-(trifluoromethyl)-1H-indol-7-yl)methoxy)methyl)piperidine-1-carboxylate (93 mg, 0.190 mmol) and potassium tert-butoxide (23.5 mg, 0.209 mmol) in tetrahydrofuran (5 ml). The reaction was stirred 1 h at ambient temperature. The reaction was quenched with water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic layers were dried with magnesium sulfate and evaporated. The residue was purified by chromatography on silica gel with a gradient of 8% to 66% ethyl acetate/hexanes. The product tert-butyl 4-(((1-methyl-5-(trifluoromethyl)-1H-indol-7-yl)methoxy)methyl)-4-phenylpiperidine-1-carboxylate (63 mg, 0.125 mmol, 65.9% yield) was obtained as a white solid. 1H-NMR (CDCl3, 400 MHz) δ 7.83 (s, 1H), 7.22-7.36 (m, 6H), 6.95 (s, 1H), 6.50 (s, 1H), 4.66 (s, 2H), 3.66 (s, 3H), 3.62 (m, 2H), 3.41 (m, 2H), 2.99 (m, 2H), 2.09 (m, 2H), 1.77 (m, 2H), 1.40 (s, 9H); Mass spec.(MH)+: 503.19.

Workup

  1. customThe reaction was quenched with water (10 mL)
  2. extractionextracted with ethyl acetate (3×10 mL)
  3. dry with materialThe combined organic layers were dried with magnesium sulfate
  4. customevaporated
  5. customThe residue was purified by chromatography on silica gel with a gradient of 8% to 66% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-9e496f6ac57b413c99be0f75a7c665b4
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Reaction notes

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