Acetic Acid → HCID 68679787, compound

HRID 2353975Notes

Reaction equation

HRID 2353975 reaction equation
COC(=O)[C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([O:11][C:12]([F:15])([F:14])[F:13])=[CH:6][C:5]=1[N:16](C(OC(C)(C)C)=O)[CH2:17][CH2:18][CH2:19][C:20]([O:22]C)=O.CC(C)([O-])C.[K+].C(O)(=O)C.C(OCC)(=O)C>C1(C)C=CC=CC=1>[CH3:10][C:8]1[C:7]([O:11][C:12]([F:13])([F:14])[F:15])=[CH:6][C:5]2[NH:16][CH2:17][CH2:18][CH2:19][C:20](=[O:22])[C:4]=2[CH:9]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8857Ethyl AcetateHCID 23665647Potassium tert-butoxideHCID 68681640HCID 68681640, compound

Product 1

HCID 68679787HCID 68679787, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

Add a solution of 2-[tert-Butoxycarbonyl-(3-methoxycarbonyl-propyl)-amino]-5-methyl-4-trifluoromethoxy-benzoic acid methyl ester (1.1 g, 2.4 mmol), in toluene (25 mL) to a solution of potassium t-butoxide (0.51 g, 4.9 mmol) in toluene (75 mL) at 100° C. over 30 min. After heating for 1 h cool the reaction to room temperature and quench the reaction with acetic acid (5.0 mmol). Dilute the reaction with ethyl acetate (100 mL) and wash with water (2×200 mL) followed by brine (200 mL). Dry the organics over sodium sulfate and remove solvent under vacuum. Dissolve the residue in acetic acid (25 mL) and dilute with concentrated HCl (15 mL) and water (10 mL). Heat the mixture at 100° C. for 2 h then cool to room temperature. While cooling in an ice bath neutralize the reaction with 5 N NaOH. Extract the organics with ethyl acetate (200 mL) and wash the organic with brine (100 mL). Remove solvent under vacuum and chromatograph the crude product over silica gel using ethyl acetate/hexane (5-20%) to elute. This provides the title compound (0.28 g, 44%) as an oil that crystallizes upon standing: H NMR (CDCl3, 400 MHz) δ 2.11-2.18 (m, 5H), 2.81 (t, J=6.8 Hz, 2H), 3.24 (t, J=6.8 Hz, 2H), 6.61 (m, 1H), 7.59 (s, 1H). MS (ES+): 260 (M+H).

Workup

  1. temperatureAfter heating for 1 h
  2. temperaturecool
  3. customthe reaction to room temperature
  4. customquench
  5. additionDilute
  6. washwash with water (2×200 mL)
  7. dry with materialDry the organics over sodium sulfate
  8. customremove solvent under vacuum
  9. dissolutionDissolve the residue in acetic acid (25 mL)
  10. additiondilute with concentrated HCl (15 mL) and water (10 mL)
  11. temperaturethen cool to room temperature
  12. temperatureWhile cooling in an ice bath
  13. customthe reaction with 5 N NaOH
  14. extractionExtract the organics with ethyl acetate (200 mL)
  15. washwash the organic with brine (100 mL)
  16. washto elute

Sources & evidence

ORD record
ord-3f9878d4fcf84cc9a1b66242b394a352
Source dataset
uspto-grants-2010_07
Patent number
US07749992B2

Reaction notes

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