Methylparaben → Methyl 4-[1-(tert-butoxycarbonyl)-4,4-difluoro-2-pyrrolidinylmethoxy]benzoate

HRID 354435Notes

Reaction equation

HRID 354435 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11]([F:14])([F:13])[CH2:10][CH:9]1[CH2:15][OH:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=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:11]([F:13])([F:14])[CH2:10][CH:9]1[CH2:15][O:16][C:18]1[CH:27]=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 7456MethylparabenHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 22001352Tert-butyl 4,4-difluoro-2-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 69332927Methyl 4-[1-(tert-butoxycarbonyl)-4,4-difluoro-2-pyrrolidinylmethoxy]benzoateYield 88.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of 1-(tert-butoxycarbonyl)-4,4-difluoro-2-pyrrolidinylmethanol (600 mg, 2.53 mmol), methyl 4-hydroxybenzoate (462 mg, 3.03 mmol), Ph3P (795 mg, 3.03 mmol) in THF (10 ml) was added DIAD (597 ul, 3.03 mmol) at room temperature. The mixture was heated at reflux for 3 h with stirring. After cooling to room temperature, the mixture was concntrated in vacuo. The residue was chromatographed on silica gel with hexane-EtOAc (4:1) as eluent to give methyl 4-[1-(tert-butoxycarbonyl)-4,4-difluoro-2-pyrrolidinylmethoxy]benzoate (831 mg, 88%) as a colorless oil. 1H-NMR (CDCl3) δ1.48 (s, 9 H), 2.53-2.61 (m, 2 H), 3.63-4.41 (series of m, total 8 H), 6.94 (d, J=8.8 Hz, 2 H), 7.99 (d, J=8.8 Hz, 2 H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3 h
  3. customThe residue was chromatographed on silica gel with hexane-EtOAc (4:1) as eluent

Sources & evidence

ORD record
ord-2e0650f0343940eca49601f57dc349cc
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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