Diisopropylethylamine → Methyl 2-(3-cyclohexyl-1,1,1-trifluoro-3-nitropropan-2-ylamino)-3,3-dimethylbutanoate

HRID 424966Notes

Reaction equation

HRID 424966 reaction equation
[F:1][C:2]([F:15])([F:14])[CH:3]=[C:4]([CH:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[N+:5]([O-:7])=[O:6].[NH2:16][C@@H:17]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:18]([O:20][CH3:21])=[O:19].C(N(C(C)C)CC)(C)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH:8]1([CH:4]([N+:5]([O-:7])=[O:6])[CH:3]([NH:16][CH:17]([C:22]([CH3:25])([CH3:24])[CH3:23])[C:18]([O:20][CH3:21])=[O:19])[C:2]([F:14])([F:15])[F:1])[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 11309583Methyl L-tert-leucinateHCID 66704837(3,3,3-Trifluoro-1-nitroprop-1-enyl)cyclohexane

Product 1

HCID 66704841Methyl 2-(3-cyclohexyl-1,1,1-trifluoro-3-nitropropan-2-ylamino)-3,3-dimethylbutanoate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (3,3,3-trifluoro-1-nitroprop-1-enyl)cyclohexane (3) (0.62 gm), (S)-methyl 2-amino-3,3-dimethylbutanoate (4) (0.656 gm, 1.3 eq) and diisopropylethylamine (0.69 mL) in toluene (15 mL) was heated to 100° C. for 23 hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, and washed successively with 1N hydrochloric acid, water, brine and then dried over anhydrous sodium sulfate. Evaporation to dryness under reduced pressure gave crude methyl 2-(3-cyclohexyl-1,1,1-trifluoro-3-nitropropan-2-ylamino)-3,3-dimethylbutanoate as a mixture of isomers. Separation by silica gel chromatography, eluting with 8% ethyl acetate/hexane, gave two fractions, a faster eluting compound, 5A-1 (0.553 gm) and a slower eluting compound, 5B-1 (0.3 gm). The two compounds are different diastereoisomers of methyl 2-(3-cyclohexyl-1,1,1-trifluoro-3-nitropropan-2-ylamino)-3,3-dimethylbutanoate (5), although the absolute stereochemistry has not yet been established.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed successively with 1N hydrochloric acid, water, brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customEvaporation to dryness under reduced pressure

Sources & evidence

ORD record
ord-3af7ca996fad45a7ae29458548ffac33
Source dataset
uspto-grants-2012_01
Patent number
US08106059B2

Reaction notes

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