Ethyl trifluoroacetate → HCID 69666019, compound

HRID 1245617Notes

Reaction equation

HRID 1245617 reaction equation
[F:1][C:2]([F:9])([F:8])[C:3](OCC)=[O:4].[H-].[Na+].[CH2:12]([O:14][C:15](=[O:30])[CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)[CH3:13]>C1COCC1>[CH2:12]([O:14][C:15](=[O:30])[CH:16]([C:3](=[O:4])[C:2]([F:9])([F:8])[F:1])[CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1)[CH3:13]

Participants

5

Reactant 3

HCID 9794Ethyl trifluoroacetate2×HCID 24758Sodium hydrideHCID 9993342Ethyl 1-((1,1-dimethylethoxy)carbonyl)-4-piperidineacetate

Product 1

HCID 69666019HCID 69666019, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
45 °C

Procedure

THF (3.0 mL) and ethyl trifluoroacetate (1.32 mL, 1.58 g, 11.1 mmol) were added to sodium hydride (442 mg of 60% oil dispersion, 11.1 mmol) in a flask fitted with a mechanical stirrer and a reflux condenser. 1-(tert-butoxycarbonyl)-4-piperidineacetic acid ethyl ester (1.50 g, 5.52 mmol) dissolved in THF (2.0 mL) was added over 30 min, with additional THF (2×1 mL) to complete the transfer. The mixture was warmed to 45° C. overnight. An additional portion of ethyl trifluoroacetate (1.0 mL, 1.19 g, 8.4 mmol) was added the temperature was increased to 70° C. for 17 h. After cooling to RT, the mixture was partitioned between EtOAc (50 mL) and a mixture of saturated aq. NaCl (25 mL) and 2 N aq. HCl (10 mL). The aqueous layer was extracted with EtOAc (25 mL). The organic layers were washed in succession with saturated aq. NaCl (2×10 mL), dried (Na2SO4), decanted, and evaporated. The crude product was purified by flash column chromatography on silica gel, eluting with 90:10 to 85:15 v/v hexanes/EtOAc to give the title compound as a colorless oil. For the title compound: 1H NMR (500 MHz, CDCl3) showed an apparent mixture of tautomers; ESI-MS 268.2 (M+H−100); HPLC A: 3.3 min.

Workup

  1. customfitted with a mechanical stirrer and a reflux condenser
  2. temperaturewas increased to 70° C. for 17 h
  3. temperatureAfter cooling to RT
  4. customthe mixture was partitioned between EtOAc (50 mL)
  5. additiona mixture of saturated aq. NaCl (25 mL) and 2 N aq. HCl (10 mL)
  6. extractionThe aqueous layer was extracted with EtOAc (25 mL)
  7. washThe organic layers were washed in succession with saturated aq. NaCl (2×10 mL)
  8. dry with materialdried (Na2SO4)
  9. customdecanted
  10. customevaporated
  11. customThe crude product was purified by flash column chromatography on silica gel
  12. washeluting with 90:10 to 85:15 v/v hexanes/EtOAc

Sources & evidence

ORD record
ord-55b6426369e044928781a0b21066b5ac
Source dataset
uspto-grants-2006_10
Patent number
US07125887B2

Reaction notes

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