3-Bromo-2-methyl-1-propene → 2-[2-[Isobutyl-(4-trifluoromethyl-phenyl)-amino]-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pent-4-enoic acid methyl ester

HRID 2427886Notes

Reaction equation

HRID 2427886 reaction equation
[CH3:1][O:2][C:3](=[O:36])[CH2:4][C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[N:8]=[C:7]([N:21]([CH2:32][CH:33]([CH3:35])[CH3:34])[C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH:6]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:48][C:49]([CH3:51])=[CH2:50]>C1COCC1>[CH3:1][O:2][C:3](=[O:36])[CH:4]([C:5]1[CH:10]=[C:9]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:15][CH:16]=2)[N:8]=[C:7]([N:21]([CH2:32][CH:33]([CH3:34])[CH3:35])[C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:29])[F:30])=[CH:24][CH:23]=2)[CH:6]=1)[CH2:50][C:49]([CH3:51])=[CH2:48]

Participants

5

Reactant 3

HCID 3577853-Bromo-2-methyl-1-propeneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 59161714[2-[Isobutyl-(4-trifluoromethyl-phenyl)-amino]-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl ester

Product 1

HCID 591617302-[2-[Isobutyl-(4-trifluoromethyl-phenyl)-amino]-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pent-4-enoic acid methyl esterYield 47.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [2-[isobutyl-(4-trifluoromethyl-phenyl)-amino]-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl ester (75 mg, 0.15 mmol) in THF (5 mL) at −78° C. under argon was added potassium bis(trimethylsilyl)amide (0.5 M solution in toluene, 300 μL, 0.15 mmol). After stirring for 30 minutes, 3-bromo-2-methylpropene (20 mg, 0.15 mmol) was added and stirred for an additional 30 minutes The reaction mixture was allowed to warm up slowly and stirred for another 30 minutes at 0° C. The mixture was then concentrated and purified by column chromatography on silica gel (0-30% methylene chloride in heptane) to give the product as a white solid (40 mg, 47%). 1H NMR (300 MHz, CDCl3) δ 8.12 (d, J=8.29 Hz, 2H), 7.71 (d, J=8.29 Hz, 2H), 7.57-7.68 (m, 2H), 7.38 (d, J=8.29 Hz, 2H), 7.19 (s, 1H), 6.55 (s, 1H), 4.61-4.79 (m, 2H), 3.96 (d, J=7.54 Hz, 2H), 3.67 (s, 3H), 2.68-2.85 (m, 1H), 2.31-2.47 (m, 1H), 2.07-2.26 (m, 1H), 1.70 (s, 3H), 0.89-1.05 (m, 6H). MS m/e 565.3 (M+H).

Workup

  1. stirringstirred for an additional 30 minutes The reaction mixture
  2. temperatureto warm up slowly
  3. stirringstirred for another 30 minutes at 0° C
  4. concentrationThe mixture was then concentrated
  5. custompurified by column chromatography on silica gel (0-30% methylene chloride in heptane)

Sources & evidence

ORD record
ord-391df11baf9b4ed58a95bddd564ad8eb
Source dataset
uspto-grants-2011_06
Patent number
US07968725B2

Reaction notes

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