Ethyl Acetate → methyl 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)benzoate

HRID 1990282Notes

Reaction equation

HRID 1990282 reaction equation
[F:1][CH:2]([F:19])[O:3][CH2:4][C@@H:5]([O:7][C:8]1[CH:9]=[C:10]([CH:15]=[C:16]([OH:18])[CH:17]=1)[C:11]([O:13][CH3:14])=[O:12])[CH3:6].[N:20]1([C:24]([C:26]2[CH:31]=[N:30][C:29](Cl)=[CH:28][N:27]=2)=[O:25])[CH2:23][CH2:22][CH2:21]1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C(#N)C>[N:20]1([C:24]([C:26]2[N:27]=[CH:28][C:29]([O:18][C:16]3[CH:15]=[C:10]([CH:9]=[C:8]([O:7][C@@H:5]([CH3:6])[CH2:4][O:3][CH:2]([F:19])[F:1])[CH:17]=3)[C:11]([O:13][CH3:14])=[O:12])=[N:30][CH:31]=2)=[O:25])[CH2:23][CH2:22][CH2:21]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 46870328(Azetidin-1-yl)(5-chloropyrazin-2-yl)methanoneHCID 59127138methyl 3-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-hydroxy-benzoate

Product 1

HCID 53629696methyl 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)benzoateYield 74.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of methyl 3-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)-5-hydroxybenzoate (0.28 g, 1.01 mmol), 2-(azetidin-1-ylcarbonyl)-5-chloropyrazine (201 mg, 1.01 mmol) and potassium carbonate (280 mg, 2.03 mmol) in acetonitrile (5 mL) was stirred in a microwave reactor at 140° C. for 5 hours. The reaction mixture was reduced in vacuo, ethyl acetate (50 mL) added and the organics washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and reduced in vacuo. The crude oil was chromatographed on silica, eluting with 20 to 70% ethyl acetate in isohexane, to give the desired compound as a colourless oil (330 mg). 1H NMR δ (CDCl3): 1.38 (d, 3H), 2.37 (quin, 2H), 3.90 (s, 3H), 3.93-4.04 (m, 2H), 4.26 (d, 2H), 4.61-4.70 (m, 3H), 6.25 (t, 1H), 6.95 (t, 1H), 7.43-7.44 (m, 1H), 7.49-7.50 (m, 1H), 8.32 (d, 1H), 8.85 (d, 1H); m/z 438 (M+H)+

Workup

  1. additionadded
  2. washthe organics washed with water (50 mL), brine (50 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customThe crude oil was chromatographed on silica
  6. washeluting with 20 to 70% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-efcd4a6837fc4c6586ef93197acb2a3b
Source dataset
uspto-grants-2010_01
Patent number
US07642259B2

Reaction notes

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