Methylparaben → methyl 4-[(2S,4S)-4-acetoxy-1-tert-butoxycarbonyl-2-pyrrolidinyl]methoxybenzoate

HRID 354426Notes

Reaction equation

HRID 354426 reaction equation
[C:1]([O:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C@H:7]([CH2:17][OH:18])[CH2:6]1)(=[O:3])[CH3:2].[CH3:19][O:20][C:21](=[O:29])[C:22]1[CH:27]=[CH:26][C:25](O)=[CH:24][CH:23]=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:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[C@H:7]([CH2:17][O:18][C:25]2[CH:26]=[CH:27][C:22]([C:21]([O:20][CH3:19])=[O:29])=[CH:23][CH:24]=2)[CH2:6]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 7456MethylparabenHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 69332993(2S,4S)-4-acetoxy-1-tert-butoxycarbonyl-2-pyrrolidinemethanol

Product 1

HCID 16093619methyl 4-[(2S,4S)-4-acetoxy-1-tert-butoxycarbonyl-2-pyrrolidinyl]methoxybenzoateYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of (2S,4S)-4-acetoxy-1tert-butoxycarbonyl-2-pyrrolidinemethanol (9.70 g, 37.4 mmol), p-hydroxybenzoic acid methyl ester (5.69 g, 37.4 mmol) and PPh3 (10.8 g, 41.1 mmol) in THF (200 ml) was added DIAD (8.10 ml, 41.1 mmol) at room temperature. After 1.5 h stirring, the mixture was concentrated in vacuo. The resulting residue was chromatographed on silica gel [700 g, CHCl3/EtOAc (10/1)], to give methyl 4-[(2S,4S)-4-acetoxy-1-tert-butoxycarbonyl-2-pyrrolidinyl]methoxybenzoate (11.8 g, 81%) as a pale yellow oil. 1H-NMR (CDCl3) δ1.48 (s, 9H), 2.03 (s, 3H), 2.27 (m, 2H), 3.46 (m, 1H), 3.72 (m, 1H), 3.88 (s, 3H), 3.98 (t, J=9.0 Hz, 1H), 4.21-4.47 (m, 2H), 5.31 (br, 1H), 6.96 (br, 2H), 7.98 (d, J=8.8 Hz, 2H).

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customThe resulting residue was chromatographed on silica gel [700 g, CHCl3/EtOAc (10/1)]

Sources & evidence

ORD record
ord-eee98a47192b4b6f8689b53cc175778e
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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