Carbonochloridic acid, 2-fluoroethyl ester → 2-fluoroethyl 3-[4-[(3aS,7aS)-2-oxo-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-1-yl]-1-piperidyl]-3-methyl-pyrrolidine-1-carboxylate

HRID 1642486Notes

Reaction equation

HRID 1642486 reaction equation
[CH3:1][C:2]1([N:7]2[CH2:12][CH2:11][CH:10]([N:13]3[C@H:17]4[CH2:18][CH2:19][CH2:20][CH2:21][C@@H:16]4[NH:15][C:14]3=[O:22])[CH2:9][CH2:8]2)[CH2:6][CH2:5][NH:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Cl[C:30]([O:32][CH2:33][CH2:34][F:35])=[O:31]>O>[O:22]=[C:14]1[N:13]([CH:10]2[CH2:11][CH2:12][N:7]([C:2]3([CH3:1])[CH2:6][CH2:5][N:4]([C:30]([O:32][CH2:33][CH2:34][F:35])=[O:31])[CH2:3]3)[CH2:8][CH2:9]2)[C@H:17]2[CH2:18][CH2:19][CH2:20][CH2:21][C@@H:16]2[NH:15]1

Participants

5

Reactant 3

HCID 10017Carbonochloridic acid, 2-fluoroethyl esterHCID 11430Potassium CarbonateHCID 57619793(3aS,7aS)-1-[1-(3-methylpyrrolidin-3-yl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one

Product 1

HCID 252212262-fluoroethyl 3-[4-[(3aS,7aS)-2-oxo-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-1-yl]-1-piperidyl]-3-methyl-pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of (3aS,7aS)-1-[1-(3-methylpyrrolidin-3-yl)-4-piperidyl]-3a,4,5,6,7,7a-hexahydro-3H-benzoimidazol-2-one (1 mmol) in water (10 mL) was added with potassium carbonate (4.0 equiv.) followed by 2-fluoroethyl chloroformate (1.2 equiv.) at room temperature and stirred at rt for 30 minutes. Extracted in ethyl acetate (2×10 mL), the combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography by eluting with methanol in ethyl acetate (0 to 5%) to afford the title compound (93 mg). 1H NMR (CD3OD, 400 MHz): δ 4.65 (t, 2H), 4.53 (t, 1H), 4.34 (m, 1H), 4.27 (m, 1H), 3.62 (m, 3H), 3.48-3.37 (m, 2H), 3.25 (t, 1H), 3.03-2.90 (m, 3H), 2.77 (br t, 1H), 2.47 (m, 3H), 1.98-1.60 (br m, 9H), 1.43 (m, 3H), 1.11 (s, 3H); MS (M+1): 397.30.

Workup

  1. extractionExtracted in ethyl acetate (2×10 mL)
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash chromatography
  6. washby eluting with methanol in ethyl acetate (0 to 5%)

Sources & evidence

ORD record
ord-f7746fb8924f48d0a716b4d9e7272458
Source dataset
uspto-grants-2012_02
Patent number
US08119661B2

Reaction notes

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