Sodium hydride → (1S,3R)-3-(4,5-Diphenylpyrimidin-2-yloxymethyl)cyclohexanecarboxylic Acid

HRID 2233322Notes

Reaction equation

HRID 2233322 reaction equation
[H-].[Na+].[OH:3][CH2:4][C@@H:5]1[CH2:10][CH2:9][CH2:8][C@H:7]([C:11]([O:13]C)=[O:12])[CH2:6]1.Cl[C:16]1[N:21]=[C:20]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:19]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:18][N:17]=1>CN(C)C=O>[C:22]1([C:20]2[C:19]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[CH:18][N:17]=[C:16]([O:3][CH2:4][C@@H:5]3[CH2:10][CH2:9][CH2:8][C@H:7]([C:11]([OH:13])=[O:12])[CH2:6]3)[N:21]=2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 126742762-Chloro-4,5-diphenylpyrimidineHCID 57350257Methyl cis-3-hydroxymethylcyclohexanecarboxylate

Product 1

HCID 68580307(1S,3R)-3-(4,5-Diphenylpyrimidin-2-yloxymethyl)cyclohexanecarboxylic AcidYield 15.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

94 mg (2.34 mmol) of sodium hydride (suspension in oil) were added to a solution of 178 mg (1.03 mmol) of methyl (1S,3R)-3-hydroxymethylcyclohexanecarboxylate in 5 ml of dimethylformamide at 0° C. After 30 minutes, a solution of 250 mg (0.94 mmol) of 2-chloro-4,5-diphenylpyrimidine in 2 ml of dimethylformamide was added. The reaction mixture was allowed to reach room temperature and was then heated at 60° C. for 2 hours. The solvent was concentrated under high vacuum and the residue was mixed with water and dichloromethane. After acidification with 1 N HCl, the aqueous phase was extracted with dichloromethane, dried and concentrated. The crude mixture was purified on silica gel with heptane/ethyl acetate (gradient 0% to 25% in 40 minutes, then isocratic for 20 minutes). 55 mg (15%) of the desired product were obtained.

Workup

  1. customto reach room temperature
  2. concentrationThe solvent was concentrated under high vacuum
  3. additionthe residue was mixed with water and dichloromethane
  4. extractionAfter acidification with 1 N HCl, the aqueous phase was extracted with dichloromethane
  5. customdried
  6. concentrationconcentrated
  7. customThe crude mixture was purified on silica gel with heptane/ethyl acetate (gradient 0% to 25% in 40 minutes
  8. waitisocratic for 20 minutes)

Sources & evidence

ORD record
ord-ea5613e00a564787816a418a4d1d3127
Source dataset
uspto-grants-2010_05
Patent number
US07709494B2

Reaction notes

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