Triethylamine → (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid methyl ester

HRID 2365744Notes

Reaction equation

Cl.[CH3:2][O:3][C:4](=[O:11])[C@@H:5]([NH2:10])[CH2:6][CH:7]([CH3:9])[CH3:8].C[O:13][C:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[C:16]=1[CH2:25]Br.C(N(CC)CC)C>C(#N)C>[CH3:2][O:3][C:4](=[O:11])[C@@H:5]([N:10]1[CH2:25][C:16]2[C:15](=[CH:20][CH:19]=[CH:18][C:17]=2[C:21]([F:24])([F:22])[F:23])[C:14]1=[O:13])[CH2:6][CH:7]([CH3:9])[CH3:8]

Participants

Conditions

Temperature: 115 °C

Procedure

A mixture of (S)-2-amino-4-methyl-pentanoic acid methyl ester hydrochloride (Aldrich, 273 mg, 1.5 mmol) and 2-bromomethyl-3-trifluoromethyl-benzoic acid methyl ester (prepared as in Example 1, 445 mg, 1.5 mmol) in acetonitrile (5 mL) and triethylamine (420 μL, 3.0 mmol) was placed in a microwave reaction vessel and sealed. The reaction mixture was then placed in a microwave reactor and heated at 115° C. for 15 min. After this time, the reaction mixture was cooled and concentrated with silica gel (2 g) in vacuo. The silica gel with absorbed material was placed in a SIM and purified via Biotage flash column chromatography (40 S silica gel column, 20% ethyl acetate/hexanes) to afford (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid methyl ester (275 mg, 56%) as a colorless viscous oil.

Workup

customwas placed in a microwave reaction vessel
customsealed
customThe reaction mixture was then placed in a microwave reactor
temperatureAfter this time, the reaction mixture was cooled
concentrationconcentrated with silica gel (2 g) in vacuo
custompurified via Biotage flash column chromatography (40 S silica gel column, 20% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-e22af16c58e54a4395ce925a084a82b9
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08697705B2

Reaction notes

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