Sodium Carbonate → 2-Ethyl-3-(1-ethylpropoxy)-6-(2-methoxy-4-trifluoromethoxyphenyl)-5-methylpyridine

HRID 1354239

Reaction equation

HRID 1354239 reaction equation
Cl[C:2]1[C:7]([O:8][CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])=[CH:6][C:5]([CH3:14])=[C:4]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][C:16]=2[O:26][CH3:27])[N:3]=1.[CH2:28](B(O)O)[CH3:29].C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:28]([C:2]1[C:7]([O:8][CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])=[CH:6][C:5]([CH3:14])=[C:4]([C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][C:16]=2[O:26][CH3:27])[N:3]=1)[CH3:29]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 521157Ethylboronic acidHCID 211047772-Chloro-3-(1-ethylpropoxy)-6-(2-methoxy-4-trifluoromethoxyphenyl)-5-methylpyridine

Product 1

HCID 98437432-Ethyl-3-(1-ethylpropoxy)-6-(2-methoxy-4-trifluoromethoxyphenyl)-5-methylpyridine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

Pd(PPh3)4 (12 mg, 0.01 mmol) is added to a solution of compound 45 (41 mg, 0.1 mmol) in toluene (0.6 ml), followed by ethylboronic acid (73 mg, 1 mmol) and Na2CO3 (1M, 0.2 ml, 0.2 mmol). The resulting mixture is heated to reflux overnight, and then cooled to room temperature. The toluene layer is separated. The aqueous layer is extracted with EtOAc. The combined organic layers are combined, washed with water, brine, dried, filtered and evaporated. The crude product is purified by chromatography (eluted with 6% EtOAc in hexane) to give the product as a white crystalline solid. 1H NMR (CDCl3) δ 1.00 (t, J=7.6 Hz, 6H), 1.23 (t, J=7.6 Hz, 3H), 1.73 (m, 4H), 2.09 (s, 3H), 2.84 (q, J=7.6 Hz, 2H), 3.87 (s, 3H), 4.16 (m, 1H), 6.78 (s, 1H), 6.89 (dd, 1H), 6.92 (s, 1H), 7.27 (d, J=8.4 Hz, 1H). LCMS 398.34 (M+1).

Workup

  1. temperatureThe resulting mixture is heated
  2. temperatureto reflux overnight
  3. customThe toluene layer is separated
  4. extractionThe aqueous layer is extracted with EtOAc
  5. washwashed with water, brine
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product is purified by chromatography (eluted with 6% EtOAc in hexane)

Sources & evidence

ORD record
ord-d0b56fd0a9dc49cd9831f4c4b1f7f91c
Source dataset
uspto-grants-2007_05
Patent number
US07223778B2

Linked notes

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