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

HRID 350385Notes

Reaction equation

HRID 350385 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 1 N 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) δ 1.39 (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 1 N 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-3deb0eb1a157404db9471fdae9eb039a
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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