Triethylamine → tert-butyl 2-[(3R*,4S*)-1-benzyl-3-{[1-(2-fluoropentyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetate

HRID 445995Notes

Reaction equation

HRID 445995 reaction equation
[CH2:1]([N:8]1[CH2:12][C@@H:11]([CH3:13])[C@@:10]([CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])([C:14]([OH:16])=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:25][CH:26]([CH2:35][CH2:36][CH3:37])[CH2:27][N:28]1[CH2:33][CH2:32][CH:31]([NH2:34])[CH2:30][CH2:29]1.C(N(CC)CC)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>O.CN(C)C=O>[CH2:1]([N:8]1[CH2:12][C@@H:11]([CH3:13])[C@@:10]([CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])([C:14](=[O:16])[NH:34][CH:31]2[CH2:32][CH2:33][N:28]([CH2:27][CH:26]([F:25])[CH2:35][CH2:36][CH3:37])[CH2:29][CH2:30]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 2724699PyBOP2×HCID 71293673(3R*,4S*)-1-Benzyl-3-[2-(tert-butoxy)-2-oxoethyl]-4-methylpyrrolidine-3-carboxylic acidHCID 866782421-(2-Fluoropentyl)piperidin-4-amine

Product 1

HCID 71293809tert-butyl 2-[(3R*,4S*)-1-benzyl-3-{[1-(2-fluoropentyl)piperidin-4-yl]carbamoyl}-4-methylpyrrolidin-3-yl]acetateYield 35.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (3R*,4S*)-1-benzyl-3-[2-(tert-butoxy)-2-oxoethyl]-4-methylpyrrolidine-3-carboxylic acid obtained in Example 1j (300 mg, 0.9 mmol), the chiral form of 1-(2-fluoropentyl)piperidin-4-amine obtained in Example 1d (182 mg, 0.967 mmol), triethylamine (0.376 ml, 2.7 mmol), PyBOP (656 mg, 1.26 mmol) and N,N-dimethylformamide (4.5 ml) was stirred at room temperature for 61 hours and 30 minutes. Triethylamine (0.207 ml, 1.49 mmol) and PyBOP (360 mg, 0.69 mmol) were further added, followed by stirring for four hours and 30 minutes. Water was added to the reaction mixture, which was extracted with ethyl acetate twice. The organic layer was washed with a saturated aqueous ammonium chloride solution and dried over anhydrous magnesium sulfate, and the solvent was distilled off. The residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/heptane) to give the title compound (161 mg, yield 35.5%).

Workup

  1. extractionwas extracted with ethyl acetate twice
  2. washThe organic layer was washed with a saturated aqueous ammonium chloride solution
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off
  5. customThe residue was purified by silica gel column chromatography (NH silica gel, elution solvent: ethyl acetate/heptane)

Sources & evidence

ORD record
ord-238abf56e8a14d1d8b0776af6eaa7c18
Source dataset
uspto-grants-2013_07
Patent number
US08476301B2

Reaction notes

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