2-Butene, 1-bromo-3-methyl- → 2-[(4-Fluoro-benzylamino)-methyl]-5-methyl-hex-4-enoic acid ethyl ester

HRID 1172375Notes

Reaction equation

HRID 1172375 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[CH2:5][CH2:6][NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:27]1([CH3:33])[CH:32]=CC=[CH:29][CH:28]=1.BrCC=C(C)C>O1CCCC1.C(=O)(O)[O-].[Na+]>[CH2:1]([O:3][C:4](=[O:16])[CH:5]([CH2:6][NH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)[CH2:29][CH:28]=[C:27]([CH3:33])[CH3:32])[CH3:2]

Participants

6

Reactant 3

HCID 700922-Butene, 1-bromo-3-methyl-HCID 4164981Ethyl 3-{[(4-fluorophenyl)methyl]amino}propanoateHCID 86583789KHMDS toluene

Product 1

HCID 576065982-[(4-Fluoro-benzylamino)-methyl]-5-methyl-hex-4-enoic acid ethyl esterYield 88%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 3-(4-fluoro-benzylamino)-propionic acid ethyl ester (158 mg, 0.701 mmol) in anhydrous tetrahydrofuran (8 mL) was stirred under an environment of nitrogen at −78° C. and treated via syringe with 0.5 M in toluene potassium bis(trimethylsilyl)-amide (1.4 mL, 0.701 mmol). After 15 min, 4-bromo-2-methyl-2-butene (104 mg, 0.701 mmol) was added and the reaction mixture was stirred at −78° C. for 6 h. The reaction was allowed to warm to 25° C. and was diluted with a saturated aqueous sodium bicarbonate solution (25 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude oil was purified by flash column chromatography (ISCO RediSep column, 5 to 60% ethyl acetate in hexanes) to give 2-[(4-fluoro-benzylamino)-methyl]-5-methyl-hex-4-enoic acid ethyl ester (181 mg, 37%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ: 1.25 (t, 3H, J=7.0 Hz), 1.60 (s, 3H), 1.68 (s, 3H), 2.18-2.25 (m, 1H), 2.28-2.37 (m, 1H), 2.55-2.62 (m, 1H), 2.69 (dd, 1H, J1=11.7 Hz, J2=4.7 Hz), 2.86 (dd, 1H, J1=11.7 Hz, J2=8.6 Hz), 3.67-3.81 (m, 2H), 4.10-4.18 (m, 2H), 5.04-5.08 (m, 1H), 6.98 (t, 2H, J=8.5 Hz), 7.23-7.27 (m, 2H). LC-MS (ESI) calculated for C17H24FNO2: 293.4, found 294.5 [M+H+].

Workup

  1. temperatureto warm to 25° C.
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. dry with materialThe combined organic layers were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude oil was purified by flash column chromatography (ISCO RediSep column, 5 to 60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-766b551cd3ba4c7ab0a2ce3c4a4d9b0d
Source dataset
uspto-grants-2010_11
Patent number
US07834009B2

Reaction notes

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