HCID 23512002, compound → HCID 23511751, compound

HRID 354322Notes

Reaction equation

HRID 354322 reaction equation
C([O:8][CH:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH:11]([CH2:21][O:22][C:23]2[CH:33]=[CH:32][C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:25][C:24]=2[O:34][CH3:35])[CH2:10]1)C1C=CC=CC=1>CCO.[Pd]>[C:17]([O:16][C:14]([N:12]1[CH2:13][CH:9]([OH:8])[CH2:10][CH:11]1[CH2:21][O:22][C:23]1[CH:33]=[CH:32][C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:25][C:24]=1[O:34][CH3:35])=[O:15])([CH3:20])([CH3:18])[CH3:19]

Participants

4

Reactant 1

HCID 23512002HCID 23512002, compound

Product 1

HCID 23511751HCID 23511751, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A stirred mixture of ethyl 4-[4-benzyloxy-1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-methoxybenzoate (1.189 g, 2.449 mmol) and 5% Pd-C (240 mg) in EtOH (10 mL) was hydrogenated overnight at room temp. The mixture was filtered to remove the catalyst and the filtrate was concentrated in vacuo to give ethyl 4-[1-(tert-butoxycarbonyl)-4-hydroxy-2-pyrrolidinyl]methoxy-3-methoxybenzoate (735.3 mg, 76%) as a pale yellow oil. To a stirred cold (minus 78° C.) solution of DAST (0.491 mL, 3.718 mmol) in CH2Cl2 (7.4 mL) was added dropwise a solution of this compound in CH2Cl2 (2 mL), and the resulting mixture was stirred overnight. The mixture was quenched with water and extracted with CHCl3. The extract was washed with brine and dried over Na2SO4. The solvent was removed under a reduced pressure and the residue was chromatographed on silica-gel with n-hexane:EtOAc (3:1, v/v) as eluent to afford 418.7 mg (57%) ethyl 4-[1-(tert-butoxycarbonyl)-4-fluoro-2-pyrrolidinyl]methoxy-3-methoxybenzoate as an oil. 1H-NMR (400 MHz, CDCl3) δ1:39 (t, J=7.3 Hz, 3H), 1.49 (s, 9H), 2.16 (br m, 1H), 2.58 (dd, J=15.6, 19.0 Hz, 1H), 3.60-3.75 (m, 2H), 3.91 (s, 3H), 3.97 (t, J=9.3 Hz, 1H), 4.35 (q, J=7.3 Hz, 2H), 4.33-4.53 (m, 2H), 5.25 (d, J=52.7 Hz, 1H), 7.04 (dd, J=7.8, 56.2 Hz, 1H), 7.55 (s, 1H), 7.65 (br s, 1H); MS (FAB) m/z 398 (M++1).

Workup

  1. filtrationThe mixture was filtered
  2. customto remove the catalyst
  3. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-79762186c4774087a123494d69a44ef5
Source dataset
uspto-grants-2004_06
Patent number
US06756378B2

Reaction notes

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