Trifluoroacetic acid → methyl 4-((2S,4S)-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoate

HRID 354410Notes

Reaction equation

HRID 354410 reaction equation
C(OC([N:8]1[CH2:12][C@@H:11]([O:13][C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=2)[CH2:10][C@H:9]1[CH2:24][O:25][C:26]1[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:22]=[CH:23][C:14]=1[O:13][C@@H:11]1[CH2:12][NH:8][C@H:9]([CH2:24][O:25][C:26]2[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=2)[CH2:10]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 16093646methyl 4-((2S,4S)-1-tert-butoxycarbonyl-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoate

Product 1

HCID 16093586methyl 4-((2S,4S)-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoateYield 114.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of methyl 4-[(2S,4S)-1-tert-butoxycarbonyl-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate (870 mg, 1.74 mmol) in CH2Cl2 (24 ml) was added TFA (6 ml) at room temperature. The mixture was stirred over night, which was concentrated in vacuo. The residue was diluted with CH2Cl2 and made basic by the addition of 1 N NaOH, which was extracted with CH2Cl2. The organic layer was washed with brine, dried over NaSO4 and concentrated. The residue was chromatographed on silica gel [100 g, n-hexane/EtOAc(2/1)], to give methyl 4-[(2S,4S)-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate (750 mg, 100%) as a black oil 1H-NMR (CDCl3) δ1.99 (dd, J=14.2, 5.6 Hz, 1H), 2.48 (m, 1H), 3.22 (dd, J=12.2, 4.6 Hz, 1H), 3.43 (d, J=12.5 Hz, 1H), 3.67 (m, 1H), 3.86 and 3.87 (s, 3H, amide isomers), 4.11 (m, 2H), 5.04 (m, 1H), 6.83 (d, J=8.5 Hz, 1H), 6.89 (d, J=8.8 Hz, 2H), 7.07 (d, J=2.0 Hz, 1H), 7.12 (d, J=9.0 Hz, 1H), 7.33 (dt, J=8.1, 1.2 Hz, 1H), 7.44 (dt, J=6.8, 1.2 Hz, 1H), 7.70 (d, J=8.1 Hz, 1H), 7.75 (dd, J=9.0, 5.1 Hz, 2H), 7.90 (d, J=8.5 Hz, 1H), 7.96 (dd, J=6.8, 2.0 Hz, 2H).

Workup

  1. concentrationwhich was concentrated in vacuo
  2. additionThe residue was diluted with CH2Cl2
  3. additionmade basic by the addition of 1 N NaOH, which
  4. extractionwas extracted with CH2Cl2
  5. washThe organic layer was washed with brine
  6. dry with materialdried over NaSO4
  7. concentrationconcentrated
  8. customThe residue was chromatographed on silica gel [100 g, n-hexane/EtOAc(2/1)]

Sources & evidence

ORD record
ord-7e3a8628a9f840b48529db6fb58606ec
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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