2-Butene, 1-bromo-3-methyl- → (S)-4-Methyl-2-(3-methyl-but-2-enylamino)-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride

HRID 990332Notes

Reaction equation

HRID 990332 reaction equation
[ClH:1].[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:21])[C@@H:15]([NH2:20])[CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:5][CH:4]=1.C(N(CC)C(C)C)(C)C.Br[CH2:39][CH:40]=[C:41]([CH3:43])[CH3:42]>C1COCC1>[ClH:1].[F:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:10][CH2:11][CH2:12][NH:13][C:14](=[O:21])[C@@H:15]([NH:20][CH2:39][CH:40]=[C:41]([CH3:43])[CH3:42])[CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 700922-Butene, 1-bromo-3-methyl-HCID 81531DiisopropylethylamineHCID 86758543(S)-2-Amino-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride

Product 1

HCID 9912978(S)-4-Methyl-2-(3-methyl-but-2-enylamino)-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochlorideYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (S)-2-amino-4-methyl-pentanoic acid [4,4-bis-(4-fluoro-phenyl)-butyl]-amide monohydrochloride (0.36 g, 0.88 mmol, Example 7) in THF (15 mL) were added, in succession, N,N-diisopropylethylamine (0.30 mL, 1.7 mmol) and 1-bromo-3-methyl-2-butene (0.10 mL, 0.87 mmol) at ambient temperature under nitrogen atmosphere. The resulting reaction mixture was stirred for 12 hours at that temperature, 16 hours at 50° C., cooled to ambient temperature, and concentrated in vacuo. The desired product was purified by flash chromatography (50% EtOAc in hexanes) and was dissolved in 10 mL of ethyl ether. To this solution was added saturated HCl solution in ethyl ether until no more white precipitate formed. Filtration and drying overnight under vacuum afforded 0.14 g (36%) of the titled compound as a yellow foam; mp 58-72° C. APCI-MS m/z 443.3 (MH+).

Workup

  1. customThe resulting reaction mixture
  2. temperaturecooled to ambient temperature
  3. concentrationconcentrated in vacuo
  4. customThe desired product was purified by flash chromatography (50% EtOAc in hexanes)
  5. dissolutionwas dissolved in 10 mL of ethyl ether
  6. additionTo this solution was added saturated HCl solution in ethyl ether until no more white precipitate
  7. customformed
  8. filtrationFiltration
  9. customdrying overnight under vacuum

Sources & evidence

ORD record
ord-e93e117dde3242fc8cdb6042b746e2df
Source dataset
uspto-grants-2002_10
Patent number
US06458781B1

Reaction notes

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