2-Butyn-1-ol → 4-(2-Butynyloxy)-5-fluoro-6-(3,5-dimethylpiperidino)pyrimidine

HRID 14556Notes

Reaction equation

HRID 14556 reaction equation
[H-].[Na+].[CH2:3]([OH:7])[C:4]#[C:5][CH3:6].F[C:9]1[C:14]([F:15])=[C:13]([N:16]2[CH2:21][CH:20]([CH3:22])[CH2:19][CH:18]([CH3:23])[CH2:17]2)[N:12]=[CH:11][N:10]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:3]([O:7][C:9]1[C:14]([F:15])=[C:13]([N:16]2[CH2:21][CH:20]([CH3:22])[CH2:19][CH:18]([CH3:23])[CH2:17]2)[N:12]=[CH:11][N:10]=1)[C:4]#[C:5][CH3:6]

Participants

6

Reactant 4

HCID 129912-Butyn-1-olHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 593411404,5-Difluoro-6-(3,5-dimethylpiperidino)pyrimidine

Product 1

HCID 593411354-(2-Butynyloxy)-5-fluoro-6-(3,5-dimethylpiperidino)pyrimidineYield 94.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

0.09 g of sodium hydride (60% oil suspension) was suspended in 3 ml of tetrahydrofuran. 0.3 ml of tetrahydrofuran solution of 0.15 g of 2-butyn-1-ol was added dropwise at room temperature therein, and the mixture was stirred for 10 minutes. Into the mixture was added dropwise 0.3 ml of tetrahydrofuran solution of 0.40 g of 4,5-difluoro-6-(3,5-dimethylpiperidino)pyrimidine (cis/trans diastereomer=about 5/1) at room temperature, and stirred for 20 minutes at 0° C. The reaction mixture was poured into a saturated ammonium chloride aqueous solution, and the mixture was extracted with tert-butyl methyl ether three times. The organic layers were washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to obtain 0.46 g of 4-(2-butynyloxy)-5-fluoro-6-(3,5-dimethylpiperidino)pyrimidine (hereinafter, referred to as Compound (51)). Compound (51) had the cis/trans diastereomer originated two methyls on the pyperidine ring. The ratio of the cis/trans diastereomer was about 5/1.

Workup

  1. stirringstirred for 20 minutes at 0° C
  2. extractionthe mixture was extracted with tert-butyl methyl ether three times
  3. washThe organic layers were washed with a saturated sodium chloride aqueous solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-0101c72b445749238c4150799afdc7bc
Source dataset
uspto-grants-2010_06
Patent number
US07732448B2

Reaction notes

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