Imidazole → Methyl 3-{2-[(1R)-1-({(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-3-[(2S)-2-(3-fluoro-4-methylbenzyl)pyrrolidin-1-yl]propyl}oxy)ethyl]phenyl}propanoate

HRID 1920792Notes

Reaction equation

HRID 1920792 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][C:32]=1[CH3:33])[CH2:5][C@@H:6]1[CH2:10][CH2:9][CH2:8][N:7]1[CH2:11][C@@H:12]([OH:29])[CH2:13][O:14][C@@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH3:16].N1C=CN=C1.[C:39]([Si:43](Cl)([CH3:45])[CH3:44])([CH3:42])([CH3:41])[CH3:40].C(OCC)(=O)C>CN(C)C=O>[Si:43]([O:29][C@H:12]([CH2:11][N:7]1[CH2:8][CH2:9][CH2:10][C@H:6]1[CH2:5][C:4]1[CH:30]=[CH:31][C:32]([CH3:33])=[C:2]([F:1])[CH:3]=1)[CH2:13][O:14][C@@H:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH2:23][CH2:24][C:25]([O:27][CH3:28])=[O:26])[CH3:16])([C:39]([CH3:42])([CH3:41])[CH3:40])([CH3:45])[CH3:44]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 8857Ethyl AcetateHCID 28928tert-Butyldimethylsilyl chlorideHCID 58581208Methyl 3-{2-[(1R)-1-({(2R)-3-[(2S)-2-(3-fluoro-4-methylbenzyl)pyrrolidin-1-yl]-2-hydroxypropyl}oxy)ethyl]phenyl}propanoate

Product 1

HCID 58581161Methyl 3-{2-[(1R)-1-({(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-3-[(2S)-2-(3-fluoro-4-methylbenzyl)pyrrolidin-1-yl]propyl}oxy)ethyl]phenyl}propanoateYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 3-{2-[(1R)-1-({(2R)-3-[(2S)-2-(3-fluoro-4-methylbenzyl)pyrrolidin-1-yl]-2-hydroxypropyl}oxy)ethyl]phenyl}propanoate (596 mg, 1.30 mmol) which had been obtained in Example 2 (2a), in N,N-dimethyl formamide was added with imidazole (221 mg, 3.25 mmol) and tert-butyl(chloro)dimethylsilane (294 mg, 1.95 mmol), and stirred at room temperature. After stirring for 24 hours, the reaction solution was added with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (n-hexane/ethyl acetate=85/15) to give the title compound as a pale yellow oily substance (676 mg, yield 91%).

Workup

  1. stirringAfter stirring for 24 hours
  2. washwashed with saturated brine
  3. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customThe residue was purified by silica gel chromatography (n-hexane/ethyl acetate=85/15)

Sources & evidence

ORD record
ord-84ef49326807416da23b9fe66997410c
Source dataset
uspto-grants-2012_05
Patent number
US08173631B2

Reaction notes

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