Sodium hydride → HCID 69003414, compound

HRID 750005Notes

Reaction equation

HRID 750005 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[H-].[Na+].[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[CH2:30]OS(C1C=CC(C)=CC=1)(=O)=O)=[O:24])([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C>[C:18]([O:22][C:23]([N:25]1[CH2:29][CH2:28][CH2:27][C@H:26]1[CH2:30][O:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:6][C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:15][CH:14]=2)=[CH:8][CH:9]=1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11783214tert-Butyl (2S)-2-(((4-methylbenzene-1-sulfonyl)oxy)methyl)pyrrolidine-1-carboxylateHCID 131220024-[(4-Chlorophenyl)methyl]phenol

Product 1

HCID 69003414HCID 69003414, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a solution of 4-(4-chloro-benzyl)-phenol (3.08 g, 14 mmol) in DMF (30 mL) at 0-5° C. was added 60% NaH (1.05 g, 26 mmol) at 0-5° C. The reaction mixture was stirred at rt for 15 min at 0-5° C. A solution of (S)-2-(Toluene-4-sulfonyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (5 g, 14 mmol) in DMF (20 mL) was added to the above mixture at 0-5° C. The reaction mixture was warmed to it and then heated at 90° C. for 15 h. The mixture was concentrated, diluted with saturated aq NaHCO3 and extracted with ethyl acetate. The aqueous layer was re-extracted with ethylacetate. The combined organic layers were dried over anhy. MgSO4 and the solvent was removed in vacuo to obtain the crude mixture, which was purified by silica gel flash chromatography to obtain the title product (1.66 g, 30%).

Workup

  1. temperatureThe reaction mixture was warmed to it
  2. temperatureheated at 90° C. for 15 h
  3. concentrationThe mixture was concentrated
  4. additiondiluted with saturated aq NaHCO3
  5. extractionextracted with ethyl acetate
  6. extractionThe aqueous layer was re-extracted with ethylacetate
  7. customThe combined organic layers were dried over anhy
  8. customMgSO4 and the solvent was removed in vacuo
  9. customto obtain the crude mixture, which
  10. customwas purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-6beb8899391f43988c845236e55a8c45
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Reaction notes

Loading…