Ammonia → HCID 54597137, compound

HRID 406130Notes

Reaction equation

HRID 406130 reaction equation
Cl.[CH3:2][C@H:3]1[CH2:7][CH2:6][CH2:5][N:4]1[C@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:18]=[CH:17][C:16]([CH2:19][C:20]([NH:22][CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)=[O:21])=[CH:15][CH:14]=2)[CH2:9]1.Cl[C:30]([O:32][CH2:33][CH3:34])=[O:31].C([O-])([O-])=O.[K+].[K+].N>C1COCC1.CO.C(Cl)Cl.O>[CH2:33]([O:32][C:30]([N:26]1[CH2:25][CH2:24][CH:23]([NH:22][C:20](=[O:21])[CH2:19][C:16]2[CH:15]=[CH:14][C:13]([N:10]3[CH2:11][CH2:12][C@H:8]([N:4]4[CH2:5][CH2:6][CH2:7][C@@H:3]4[CH3:2])[CH2:9]3)=[CH:18][CH:17]=2)[CH2:28][CH2:27]1)=[O:31])[CH3:34]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 71280830HCID 71280830, compound

Product 1

HCID 54597137HCID 54597137, compoundYield 69%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

2-[4-((2S,3′S)-2-Methyl-[1,3′]bipyrrolidinyl-1′-yl)-phenyl]-N-piperidin-4-yl-acetamide hydrochloride (0.51 g, 1.38 mmol) was dissolved in THF (20 mL) and water (5 mL) to form a clear solution. To this solution was added 0.30 g of ethyl chloroformate (3 mmol, 2 equiv), followed by K2CO3 (0.76 g, 5.52 mmol, 4 equiv). The clear solution was stirred at rt overnight. TLC (5% of 7N NH3 in MeOH/DCM) showed the SM was consumed completely. LCMS: a single peak at 2.559 with MS of 443 was detected. The two layers were separated and the aqueous layer was extracted with EtOAc (2×10 mL). The combined organic solution was washed with brine (2×10 mL), dried (K2CO3), filtered, and concentrated. The crude product was purified on a 25-g silica gel column to get 0.42 g (69%) of the title compound as a tan solid.

Workup

  1. customwas consumed completely
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×10 mL)
  4. washThe combined organic solution was washed with brine (2×10 mL)
  5. dry with materialdried (K2CO3)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified on a 25-g silica gel column

Sources & evidence

ORD record
ord-5e6d6ec4555f43c4bd54eb05eb139ffd
Source dataset
uspto-grants-2014_06
Patent number
US08754095B2

Reaction notes

Loading…