Sodium Hydroxide → 4-Chloro-2-cyclopentyl-6-(trifluoromethyl)pyrimidine

HRID 1508937Notes

Reaction equation

HRID 1508937 reaction equation
[CH:1]1([C:6]2[N:11]=[C:10](O)[CH:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.O=P(Cl)(Cl)[Cl:19].[OH-].[Na+]>>[Cl:19][C:10]1[CH:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[N:7]=[C:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[N:11]=1

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 1785161402-cyclopentyl-6-(trifluoromethyl)-1H-pyrimidin-4-one

Product 1

HCID 901130984-Chloro-2-cyclopentyl-6-(trifluoromethyl)pyrimidineYield 90%

Conditions

Temperature
75 °C

Procedure

2-Cyclopentyl-6-(trifluoromethyl)pyrimidin-4-ol (2.2 g, 9.47 mmol) was suspended in POCl3 (8.8 ml, 94.7 mmol) and heated to 75° C. for 2 h. After this time, the mixture was added to a chilled sodium hydroxide solution (1 M) and then extracted with ethyl acetate. The organic layer were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound (2.1 g, 90%) as a clear oil. MW=250.65. 1H NMR (CDCl3, 500 MHz) δ 7.46 (s, 1H), 3.42 (quin, J=8.2 Hz, 1H), 2.18-2.07 (m, 2H), 1.99-1.80 (m, 4H), 1.76-1.66 (m, 2H); APCI MS m/z 251 [M+H]+.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer were dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified by column chromatography (silica, hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-bb5a227ea5c04ea3903561b3031b8a59
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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