2-Butyn-1-ol → HCID 59341145, compound

HRID 14557Notes

Reaction equation

HRID 14557 reaction equation
[H-].[Na+].[CH2:3]([OH:7])[C:4]#[C:5][CH3:6].[Cl:8][C:9]1[C:10](F)=[N:11][C:12]([F:23])=[N:13][C:14]=1[N:15]1[CH2:20][CH:19]([CH3:21])[CH2:18][CH:17]([CH3:22])[CH2:16]1.[Cl-].[NH4+]>O1CCCC1>[Cl:8][C:9]1[C:10]([O:7][CH2:3][C:4]#[C:5][CH3:6])=[N:11][C:12]([F:23])=[N:13][C:14]=1[N:15]1[CH2:20][CH:19]([CH3:21])[CH2:18][CH:17]([CH3:22])[CH2:16]1

Participants

6

Reactant 4

HCID 129912-Butyn-1-olHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 59341122HCID 59341122, compound

Product 1

HCID 59341145HCID 59341145, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

0.09 g of sodium hydride (60% oil suspension) was suspended in 2 ml of tetrahydrofuran. 0.3 ml of tetrahydrofuran solution of 0.13 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 0.4 g of 5-chloro-2,4-difluoro-6-(3,5-dimethylpiperidino) pyrimidine at 0° C., and stirred for 30 minutes at same temperature. 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 0.20 g of 5-chloro-4-(2-butynyloxy)-2-fluoro-6-(3,5-dimethyl piperidino)pyrimidine (hereinafter, referred to as Compound (52)). Compound (52) 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 30 minutes at same temperature
  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-f043f5a3361b45a9a972519bc0f9c7f8
Source dataset
uspto-grants-2010_06
Patent number
US07732448B2

Reaction notes

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