Trifluoroacetic acid → Ethyl 4-(4-fluoro-2-pyrrolidinyl)methoxy-3-methoxybenzoate

HRID 354323Notes

Reaction equation

HRID 354323 reaction equation
C(OC([N:8]1[CH2:12][CH:11]([F:13])[CH2:10][CH:9]1[CH2:14][O:15][C:16]1[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][C:17]=1[O:27][CH3:28])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:13][CH:11]1[CH2:12][NH:8][CH:9]([CH2:14][O:15][C:16]2[CH:26]=[CH:25][C:19]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:18][C:17]=2[O:27][CH3:28])[CH2:10]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 23512237HCID 23512237, compound

Product 1

HCID 23512277Ethyl 4-(4-fluoro-2-pyrrolidinyl)methoxy-3-methoxybenzoateYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of ethyl 4-[1-(tert-butoxycarbonyl)4-fluoro-2-pyrrolidinyl]methoxy-3-methoxybenzoate (482.2 mg, 1.213 mmol) in CH2Cl2 (10.0 mL) was added TFA (1.9 mL) at 0° C., and the mixture was stirred at room temp for 2 hr. The solvent was removed under a reduced pressure and the residue was made basic by the addition of 1N NaOH and extracted with CHCl3. The extract was washed with brine, dried over Na2SO4, and concentrated under a reduced pressure to afford 348.7 mg (97%) ethyl 4-(4-fluoro-2-pyrrolidinyl)methoxy-3-methoxybenzoate as a brownish oil. 1H-NMR (400 MHz, CDCl3) δ1.39 (t, J=6.8 Hz, 3H), 1.97 (ddt, J=1.5, 5.4, 14.7 Hz, 1H), 2.27 (dddd, J=5.9, 8.8, 14.7, 32.7 Hz, 1H), 3.02 (ddd, J=3.9, 13.1, 35.2 Hz, 1H), 3.36 (dd, J=12.7, 21.5 Hz, 1H), 3.65 (m, 1H), 3.90 (s, 3H), 4.09 (m, 1H), 4.35 (q, J=6.8 Hz, 2H), 5.17, 5.31 (br m each, 1H), 6.90 (d, J=8.3 Hz, 1H), 7.75 (d, J=2.0 Hz, 1H), 7.65 (dd, J=2.0, 8.3 Hz, 1H); MS (FAB) m/z 298 (M++1).

Workup

  1. customThe solvent was removed under a reduced pressure
  2. additionthe residue was made basic by the addition of 1N NaOH
  3. extractionextracted with CHCl3
  4. washThe extract was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under a reduced pressure

Sources & evidence

ORD record
ord-c5ddbe27813148479c3301f24ae02c4e
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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