Methylparaben → Methyl 4-(1-(tert-butoxycarbonyl)-4-(2,4-difluorophenoxy)-2-pyrrolidinyl methoxy]benzoate

HRID 354405Notes

Reaction equation

HRID 354405 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[CH2:10][CH:9]1[CH2:22][OH:23])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[C:25]1[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=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][CH:11]([O:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[CH2:10][CH:9]1[CH2:22][O:23][C:25]1[CH:34]=[CH:33][C:28]([C:29]([O:31][CH3:32])=[O:30])=[CH:27][CH:26]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 7456MethylparabenHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 69333353HCID 69333353, compound

Product 1

HCID 69333033Methyl 4-(1-(tert-butoxycarbonyl)-4-(2,4-difluorophenoxy)-2-pyrrolidinyl methoxy]benzoateYield 75.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 1-(tert-butoxycarbonyl)-4-(2,4-difluorophenoxy)-2-pyrrolidinylmethanol (500 mg, 1.52 mmol), methyl 4-hydroxybenzoate (277 mg, 1.82 mmol), and Ph3P (477 mg, 1.82 mmol) in THF (10 ml) was added DIAD (358 ul, 1.82 mmol), and the mixture was heated at reflux for 5 h. After cooling to room temperature, the mixture was concentrated in vacuo and the residue was chromatographed on silica gel with CHCl3-EtOAc (20:1) as eluent to give methyl 4-[1-(tert-butoxycarbonyl)-4-(2,4-difluorophenoxy)-2-pyrrolidinylmethoxy]benzoate (529 mg, 75%) as a colorless oil. 1H-NMR (CDCl3) δ1.46 (s, 9 H), 2.20-2.47 (m, 2 H), 3.64 (m, 2 H), 3.86 (s, 3 H), 4.07-4.43 (m, 3 H), 4.86 (m, 1 H), 6.74-6.87 (m, 3 H), 6.94 (d, 2 H, J=8.5 Hz), 7.95 (d, 2 H, J=8.5 Hz).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 5 h
  3. concentrationthe mixture was concentrated in vacuo
  4. customthe residue was chromatographed on silica gel with CHCl3-EtOAc (20:1) as eluent

Sources & evidence

ORD record
ord-4d97f7e10caf4930826d13e15bae5dfd
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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