Sodium hydride → (5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzyloxy)-acetic acid tert-butyl ester

HRID 11643Notes

Reaction equation

HRID 11643 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:29]=[CH:28][C:7]([O:8][CH2:9][C:10]([N:12]2[CH2:17][C@H:16]([CH3:18])[N:15]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[CH2:14][C@H:13]2[CH3:27])=[O:11])=[C:6]([CH2:30][OH:31])[CH:5]=1.Br[CH2:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35]>O1CCCC1>[C:37]([O:36][C:34](=[O:35])[CH2:33][O:31][CH2:30][C:6]1[CH:5]=[C:4]([Cl:3])[CH:29]=[CH:28][C:7]=1[O:8][CH2:9][C:10]([N:12]1[CH2:17][C@H:16]([CH3:18])[N:15]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH2:14][C@H:13]1[CH3:27])=[O:11])([CH3:40])([CH3:39])[CH3:38]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 545634622-[4-Chloro-2-(hydroxymethyl)phenoxy]-1-{(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl}ethan-1-one

Product 1

HCID 69655425(5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-benzyloxy)-acetic acid tert-butyl esterYield 65.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a 0° C. solution of sodium hydride (0.025 g, 60% dispersion, 1.0 mmol) in tetrahydrofuran (2 mL) was added a solution of 2-(4-chloro-2-hydroxymethyl-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-ethanone (0.17 g, 0.40 mmol) and tert-butyl bromoacetate (0.23 g, 3.0 mmol) in tetrahydrofuran (2 mL). The reaction mixture was warmed to ambient temperature overnight, quenched with water and diluted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated in vacuo. The crude product was purified via chromatography on silica gel to give the title compound (0.14 g).

Workup

  1. customquenched with water
  2. additiondiluted with ethyl acetate
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified via chromatography on silica gel

Sources & evidence

ORD record
ord-97b235d71bf44205a4006c9047c4a223
Source dataset
uspto-grants-2006_08
Patent number
US07098212B2

Reaction notes

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