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

HRID 2427873Notes

Reaction equation

HRID 2427873 reaction equation
[CH3:1][O:2][C:3](=[O:28])[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]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)[CH:6]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:40][C:41]([CH3:43])=[CH2:42]>C1COCC1>[CH3:1][O:2][C:3](=[O:28])[CH:4]([C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:20])[F:19])=[CH:13][CH:12]=2)[N:8]=[C:7]([C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)[CH:6]=1)[CH2:42][C:41]([CH3:43])=[CH2:40]

Participants

5

Reactant 3

HCID 3577853-Bromo-2-methyl-1-propeneHCID 3251421Potassium bis(trimethylsilyl)amideHCID 59161733[2-(4-Fluoro-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl ester

Product 1

HCID 591617282-[2-(4-Fluoro-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-4-methyl-pent-4-enoic acid methyl esterYield 60.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of [2-(4-fluoro-phenyl)-6-(4-trifluoromethyl-phenyl)-pyridin-4-yl]-acetic acid methyl ester (130 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 30 additional 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 (0-8% ethyl acetate in heptane) to give the product as a colorless oil (80 mg, 60%). 1H NMR (300 MHz, CDCl3) δ 8.23 (d, J=8.29 Hz, 2H), 8.08-8.18 (m, 2H), 7.75 (d, J=8.29 Hz, 2H), 7.67 (d, J=1.88 Hz, 2H), 7.19 (t, J=8.85 Hz, 2H), 4.78 (d, J=18.08 Hz, 2H), 3.95 (dd, J=6.78, 9.04 Hz, 1H), 3.72 (s, 3H), 2.94 (dd, J=9.04, 14.69 Hz, 1H), 2.55 (dd, J=6.40, 14.69 Hz, 1H), 1.77 (s, 3H). MS m/e 444.3 (M+H).

Workup

  1. stirringstirred for 30 additional 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 (0-8% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-bffeaae24b9b4bcd9e84d454344b5687
Source dataset
uspto-grants-2011_06
Patent number
US07968725B2

Reaction notes

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