Trifluoroacetic acid → dimethyl (S)-4-(2-pyrrolidinylmethoxy)phthalate

HRID 354289Notes

Reaction equation

HRID 354289 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[C:17]([C:25]([O:27][CH3:28])=[O:26])[C:18](=[CH:23][CH:24]=1)[C:19]([O:21][CH3:22])=[O:20])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][C:15]1[CH:16]=[C:17]([C:25]([O:27][CH3:28])=[O:26])[C:18](=[CH:23][CH:24]=1)[C:19]([O:21][CH3:22])=[O:20]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86587781dimethyl (S)-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinylmethoxy]phthalate

Product 1

HCID 86595075dimethyl (S)-4-(2-pyrrolidinylmethoxy)phthalateYield 18.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of dimethyl (S)-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinylmethoxy]phthalate (5.75 g, 14.62 mmol) in CH2Cl2 (25 mL) was added TFA (20 mL), and the resulting mixture was stirred for 50 min at room temp. The resulting mixture was concentrated in vacuo and made basic with sat. NaHCO3. The mix was extracted with CH2Cl2, washed with brine, dried over MgSO4, and evaporated off in vacuo. The residue was purified by column chromatography on silica-gel with CHCl3—MeOH (50:1, v/v) as eluent to give 790 mg (18%) dimethyl (S)-4-(2-pyrrolidinylmethoxy)phthalate as a brown oil. 1H-NMR (CDCl3) δ1.48-1.57 (m, 1 H), 1.72-1.84 (m, 2 H), 1.89-1.98 (m, 2 H), 2.91-3.03 (m, 2 H), 3.48-3.54 (m, 1 H), 3.82-3.97 (m, total 8 H), 6.98 (dd, 1 H, J=2.4, 8.8 Hz), 7.06 (d, 1 H, J=2.4 Hz), 7.78 (d, 1 H, J=8.8 Hz).

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. extractionThe mix was extracted with CH2Cl2
  3. washwashed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated off in vacuo
  6. customThe residue was purified by column chromatography on silica-gel with CHCl3—MeOH (50:1

Sources & evidence

ORD record
ord-162e2812dd894409922269ef404d9bac
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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