Sodium hydride → (4-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazol-4-yl)methanol

HRID 251456Notes

Reaction equation

HRID 251456 reaction equation
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][CH2:9][OH:10].[H-].[Na+].Cl[C:14]1[N:19]=[CH:18][C:17]([C:20]2[O:21][CH2:22][C:23]([CH2:26][OH:27])([CH3:25])[N:24]=2)=[CH:16][CH:15]=1>CN(C=O)C.C(OCC)(=O)C>[CH3:25][C:23]1([CH2:26][OH:27])[CH2:22][O:21][C:20]([C:17]2[CH:18]=[N:19][C:14]([O:10][CH2:9][CH2:8][CH2:7][N:3]3[CH2:4][CH2:5][CH2:6][CH:2]3[CH3:1])=[CH:15][CH:16]=2)=[N:24]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 11950723[2-(6-Chloropyridin-3-yl)-4-methyl-4,5-dihydro-1,3-oxazol-4-yl]methanolHCID 224016093-(2-Methylpyrrolidin-1-yl)propan-1-ol

Product 1

HCID 11950724(4-Methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazol-4-yl)methanolYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-(2-methylpyrrolidin-1-yl)propan-1-ol (1.9 g, 13.4 mmol) in dry DMF (40 ml) is treated at 0° C. with sodium hydride (60% dispersion in mineral oil, 536 mg, 13.4 mmol) and stirred 15 minutes at 0° C. Then, a solution of [2-(6-chloropyridin-3-yl)-4-methyl-4,5-dihydro-1,3-oxazol-4-yl]methanol ax55 (1.8 g, 7.9 mmol) in dry DMF (40 ml) is added dropwise over 15 minutes and the resulting mixture is stirred at room temperature for 1 day. The mixture is then poured into ice-cold water (250 ml) and extracted with ethyl acetate (4×50 ml). The organic layers are combined, dried over sodium sulfate and concentrated. The residue is dried under high-vacuum with heating to leave a solid. This solid is taken up in ethyl acetate, washed with brine and filtered. After phase separation, the aqueous layer is extracted twice with ethyl acetate, the combined organic phases are washed three times with water, dried over magnesium sulfate and concentrated to afford 1.4 g of 80% pure (4-methyl-2-{6-[3-(2-methylpyrrolidin-1-yl)propoxy]pyridin-3-yl}-4,5-dihydro-1,3-oxazol-4-yl)methanol ax56.

Workup

  1. stirringthe resulting mixture is stirred at room temperature for 1 day
  2. extractionextracted with ethyl acetate (4×50 ml)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue is dried under high-vacuum
  6. temperaturewith heating
  7. customto leave a solid
  8. washwashed with brine
  9. filtrationfiltered
  10. customAfter phase separation
  11. extractionthe aqueous layer is extracted twice with ethyl acetate
  12. washthe combined organic phases are washed three times with water
  13. dry with materialdried over magnesium sulfate
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-be4db4661f71492eaf46b957e000474b
Source dataset
uspto-grants-2011_01
Patent number
US07863450B2

Reaction notes

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