3-Bromo-2-methyl-1-propene → 2-[2-(3,5-Bis-trifluoromethyl-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pent-4-enoic acid methyl ester

HRID 2427878Notes

Reaction equation

HRID 2427878 reaction equation
[CH3:1][O:2][C:3](=[O:35])[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]([C:21]2[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=2)[CH:6]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:47][C:48]([CH3:50])=[CH2:49]>C1COCC1>[CH3:1][O:2][C:3](=[O:35])[CH:4]([C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][CH:12]=2)[N:8]=[C:7]([C:21]2[CH:22]=[C:23]([C:31]([F:33])([F:34])[F:32])[CH:24]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:26]=2)[CH:6]=1)[CH2:49][C:48]([CH3:50])=[CH2:47]

Participants

5

Reactant 3

HCID 3577853-Bromo-2-methyl-1-propeneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 59161719[2-(3,5-Bis-trifluoromethyl-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl ester

Product 1

HCID 591617112-[2-(3,5-Bis-trifluoromethyl-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pent-4-enoic acid methyl esterYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [2-(3,5-bis-trifluoromethyl-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl ester (150 mg, 0.3 mmol) in THF (5 mL) at −78° C. under argon was added potassium bis(trimethylsilyl)amide (0.5 M solution in toluene, 600 μL, 0.3 mmol). After stirring for 30 minutes, 3-bromo-2-methylpropene (40 mg, 0.3 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 (20-60% methylene chloride in heptane) to give the product as a white solid (85 mg, 51%). 1H NMR (300 MHz, CDCl3) δ 8.56 (s, 2H), 8.23 (d, J=8.29 Hz, 2H), 7.96 (s, 1H), 7.69-7.86 (m, 4H), 4.80 (d, J=19.59 Hz, 2H), 4.01 (dd, J=6.78, 9.04 Hz, 1H), 3.74 (s, 3H), 2.97 (dd, J=9.04, 14.69 Hz, 1H), 2.58 (dd, J=6.78, 14.69 Hz, 1H), 1.79 (s, 3H). MS m/e 562.2 (M+H).

Workup

  1. stirringstirred for an additional 30 minutes
  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 (20-60% methylene chloride in heptane)

Sources & evidence

ORD record
ord-79bfedeb3e5a457c9307f4d208d189a8
Source dataset
uspto-grants-2011_06
Patent number
US07968725B2

Reaction notes

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