1,1,2-Trichloroethane → HCID 66759754, compound

HRID 889202Notes

Reaction equation

HRID 889202 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[N:10]=[CH:9][C:8]([CH2:11][CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:7][CH:6]=1)=[O:4].[Cl:20]C(Cl)CCl.[H][H].Cl.CO>CO.O=[Pt]=O>[CH3:1][NH:2][C:3]([CH:5]1[NH:10][CH2:9][CH:8]([CH2:11][CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7][CH2:6]1)=[O:4].[ClH:20]

Participants

7

Reactant 4

HCID 65741,1,2-TrichloroethaneHCID 21893726Hydrochloride methanolHCID 66759944HCID 66759944, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 66759754HCID 66759754, compoundYield 111.6%

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 887MethanolSolvent

Procedure

A mixture of tert-butyl 3-(6-(methylcarbamoyl)pyridin-3-yl)propanoate (2.16 g, 8.18 mmol), PtO2 (0.40 g) and 1,1,2-trichloroethane (1.0 mL, 12.4 mmol) in methanol (50 mL) was placed in Parr reactor under 70 psi hydrogen atmosphere for 3.5 days. To the mixture was added 1.25 N HCl/MeOH (6 mL, 7.5 mmol) and the reaction was allowed to continue overnight. The reaction was filtered and evaporated to dryness to give tert-butyl 3-(6-(methylcarbamoyl)piperidin-3-yl)propanoate/HCl salt as a foamy solid (2.80 g). LCMS (+APCI) 271 (M+). The solid give tert-butyl 3-(6-(methylcarbamoyl)piperidin-3-yl)propanoate/HCl was mixed with dichloromethane (100 mL) at 0° C. and to this mixture was added DIPEA (diisopropylethylamine) (6.37 mL) and trifluoroacetic anhydride (3.44 g, 16.4 mmol) with stirring for 30 min. The mixture was warmed to room temperature, stirred for 30 min and evaporated to dryness. The crude was neutralized with a saturated aqueous sodium bicarbonate solution (100 mL) and extracted with ethyl acetate. Evaporation gave tert-butyl 3-(6-(methylcarbamoyl)-1-(2,2,2-trifluoroacetyl)piperidin-3-yl)propanoate as an oil that was purified by silica chromatography eluting with a gradient of 5% to 100% EtOAc/Hex then 0% to 10% MeOH/EtOAc to give 0.84 g of the ester as an oil. LCMS (+APCI) 367 (M+1).

Workup

  1. filtrationThe reaction was filtered
  2. customevaporated to dryness

Sources & evidence

ORD record
ord-195463f953114d9ba19b9152cb276391
Source dataset
uspto-grants-2012_08
Patent number
US08252793B2

Reaction notes

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