Sodium Bicarbonate → (R)-1-[1-(4-Chloro-phenyl)-cyclobutanecarbonyl]-piperidine-3-carboxylic acid ethyl ester

HRID 720039Notes

Reaction equation

HRID 720039 reaction equation
C([C@@H]([C@H](C(O)=O)O)O)(O)=O.[NH:11]1[CH2:21][CH2:20][CH2:19][C@@H:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12]1.C(=O)(O)[O-].[Na+].[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2([C:38](Cl)=[O:39])[CH2:37][CH2:36][CH2:35]2)=[CH:30][CH:29]=1>ClCCl>[CH2:17]([O:16][C:14]([C@@H:13]1[CH2:19][CH2:20][CH2:21][N:11]([C:38]([C:34]2([C:31]3[CH:30]=[CH:29][C:28]([Cl:27])=[CH:33][CH:32]=3)[CH2:35][CH2:36][CH2:37]2)=[O:39])[CH2:12]1)=[O:15])[CH3:18]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 130833731-(4-Chlorophenyl)cyclobutane-1-carbonyl chlorideHCID 14183616Ethyl (R)-Nipecotate L-Tartrate

Product 1

HCID 58737402(R)-1-[1-(4-Chloro-phenyl)-cyclobutanecarbonyl]-piperidine-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethyl (R)-nipecotate L-tartrate (15.0 g, 48.8 mmol) was added to a stirred mixture of dichloromethane and saturated sodium bicarbonate solution (100 mL each) at 0° C. After 10 min 1-(4-chloro-phenyl)-cyclobutanecarbonyl chloride (11.13 g, 48.8 mmol) was slowly added at 0° C. The reaction was then allowed to stir for 2 h at room temperature. The organic layer was separated and the aqueous layer was washed once with dichloromethane (100 mL). The organic material was combined and washed once with water (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated by rotary evaporation. The residue was purified by chromatography on silica gel, eluting with hexane/ethyl acetate (2:1) to give 9.2 g of the amidester as a thick clear gum; C19H24ClNO3, LRMS (m/z)=350 (MH+).

Workup

  1. customThe organic layer was separated
  2. washthe aqueous layer was washed once with dichloromethane (100 mL)
  3. washwashed once with water (100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customThe residue was purified by chromatography on silica gel
  8. washeluting with hexane/ethyl acetate (2:1)
  9. customto give 9.2 g of the amidester as a thick clear gum

Sources & evidence

ORD record
ord-41cd7a18114741179a5d1825135fdcbb
Source dataset
uspto-grants-2006_11
Patent number
US07132551B2

Reaction notes

Loading…