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

HRID 350473Notes

Reaction equation

HRID 350473 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(211)], to give methyl 4-[(2S, 4S)-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate (750 mg, 100%) as a black oil 1H-NMR (CDCl3) δ 1.99 (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, 2).

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(211)]

Sources & evidence

ORD record
ord-2fe1691bdf2949399113ae3890df8544
Source dataset
uspto-grants-2007_02
Patent number
US07179819B2

Reaction notes

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