Morpholine → HCID 86633639, compound

HRID 1855524Notes

Reaction equation

HRID 1855524 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[N:13]=[C:12]([C:14]([OH:16])=O)[CH:11]=[C:10]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)[N:9]=1.[NH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.C(=O)([O-])O.[Na+]>ClCCl.CN(C)C=O>[Cl:7][C:8]1[N:13]=[C:12]([C:14]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:16])[CH:11]=[C:10]([C:17]2[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=2)[N:9]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 86633637HCID 86633637, compound

Product 1

HCID 86633639HCID 86633639, compoundYield 69.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

Oxalyl chloride (0.38 mL, 4.5 mmol) and N,N-dimethylformamide (0.03 mL) were added to a suspension of 2-chloro-6-(4-trifluoromethyl-phenyl)-pyrimidine-4-carboxylic acid (303 mg, 1.0 mmol) in dichloromethane (20 mL). The mixture was stirred at 20° C. for 3 h and then evaporated under reduced pressure. The residue was dissolved in dichloro-methane (25 mL) and the solution was stirred together morpholine (0.174 mL, 2.0 mmol) and saturated aqueous sodium hydrogencarbonate solution (8 mL) for 1 h at 20° C. The mixture was diluted with dichloromethane (25 mL), and the organic layer was washed with water and brine, dried over sodium sulfate, and evaporated under reduced pressure. The residual material was purified by chromatography on silica gel using heptane/0-40% ethyl acetate as eluent to give the title compound (260 mg, 66%) as a white solid. MS ISP (m/e): 372.2 [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=8.25 (d, 2H), 8.04 (s, 1H), 7.80 d, 2H), 3.83 (br s, 4H), 3.74 (m, 4H).

Workup

  1. customevaporated under reduced pressure
  2. dissolutionThe residue was dissolved in dichloro-methane (25 mL)
  3. washthe organic layer was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated under reduced pressure
  6. customThe residual material was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-9e2dbf333a3045298a731414fb068565
Source dataset
uspto-grants-2015_02
Patent number
US08962834B2

Reaction notes

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