Hydrochloric Acid → HCID 69673052, compound

HRID 1426319Notes

Reaction equation

HRID 1426319 reaction equation
[Br:1]Br.[CH:3]1([C:7]2[N:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:10]=[C:9]([C:17]([O:19]CC)=[O:18])[CH:8]=2)[CH2:6][CH2:5][CH2:4]1.O.[OH-].[Li+].Cl>C(O)(=O)C.O>[Br:1][C:3]1([C:7]2[N:12]=[C:11]([C:13]([F:16])([F:15])[F:14])[N:10]=[C:9]([C:17]([OH:19])=[O:18])[CH:8]=2)[CH2:6][CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24408BromineHCID 168937Lithium hydroxide, monohydrateHCID 69672849HCID 69672849, compound

Product 1

HCID 69673052HCID 69673052, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Conditions

Temperature
80 °C

Procedure

Bromine (0.13 mL, 2.6 mmol) was added to a solution of ethyl 6-cyclobutyl-2-(trifluoromethyl)pyrimidine-4-carboxylate (0.65 g, 2.4 mmol, from Step B) in acetic acid (2.0 mL) and the reaction was heated to 80° C. for one hour. The mixture was concentrated and the resulting oil was dissolved in THF (8.0 mL) and cooled to 0° C. A solution of lithium hydroxide, monohydrate (0.20 g, 4.7 mmol) in water (2.0 mL) was added. After stirring for 20 minutes, 1N HCl was added to achieve pH 4. Additional water was introduced and the product was extracted with six portions of 10% isopropanol in chloroform. The combined extracts were dried over sodium sulfate, filtered and concentrated to afford product which was used without further purification (0.64 g, 80%). H NMR (400 MHz, dmso) δ 8.27 (s, 1H), 3.17-2.97 (m, 2H), 2.92-2.71 (m, 2H), 2.34 (dtt, J=10.9, 9.1, 6.9 Hz, 1H), 1.84 (dtt, J=11.0, 8.6, 5.6 Hz, 1H); LCMS (M+H)+: 324.9, 326.7.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe resulting oil was dissolved in THF (8.0 mL)
  3. temperaturecooled to 0° C
  4. extractionthe product was extracted with six portions of 10% isopropanol in chloroform
  5. dry with materialThe combined extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford product which
  9. customwas used without further purification (0.64 g, 80%)

Sources & evidence

ORD record
ord-4a84432edcdd454f99e27641ae5628bf
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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