Methylparaben → methyl 4-((2S,4S)-1-tert-butoxycarbonyl-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoate

HRID 354409Notes

Reaction equation

HRID 354409 reaction equation
[C:1]([O:5][C:6]([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][OH:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:1]([O:5][C:6]([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:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 7456MethylparabenHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 67405321(2S,4S)-1-tert-butoxycarbonyl-4-(2-naphthyloxy)-2-pyrrolidinylmethanol

Product 1

HCID 16093646methyl 4-((2S,4S)-1-tert-butoxycarbonyl-4-(2-naphthyloxy)-2-pyrrolidinylmethoxy)benzoateYield 93.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of (2S,4S)-1-tert-butoxycarbonyl-4-(2-naphthyloxy)-2-pyrrolidinylmethanol (640 mg, 1.86 mmol), methyl 4-hydroxybenzoate (283 mg, 1.86 mmol) and PPh3 (488 mg, 1.86 mmol) in THF (18 ml) was added DIAD (0.37 ml, 1.86 mmol) at room temperature under an atmosphere of nitrogen. The mixture was stirred over night. After removal of the solvent, the resulting residue was chromatographed on silica gel [100 g, n-hexane/EtOAc(2/1)], to give methyl 4-[(2S,4S)-1-tert-butoxycarbonyl-4-(2-naphthyloxy)-2-pyrrolidinyl]methoxybenzoate (830 mg, 93%) as a colorless oil. 1H-NMR (CDCl3) δ1.50 (d, J=8.3 Hz, 9H), 2.34 (m, 1H), 2.53 (d, J=14.2 Hz, 1H), 3.72-3.85 (m, 1H), 3.86 and 3.87 (s, 3H, amide isomers), 4.17 (m, 1H), 4.26-4.52 (m, 2H), 5.06 (br, 1H), 6.87 (d, J=8.8 Hz, 1H), 6.94 (d, J=8.8 Hz, 2H), 7.04 (br, 2H), 7.33 (t, J=7.3 Hz, 1H), 7.42 (t, J=7.3 Hz, 1H), 7.64-8.02 (m, 5H).

Workup

  1. customAfter removal of the solvent
  2. customthe resulting residue was chromatographed on silica gel [100 g, n-hexane/EtOAc(2/1)]

Sources & evidence

ORD record
ord-39cba7a2a7fe46a180042fcfbbb58fb1
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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