Isopropanol → 4-Methyl-benzenesulfinic acid[2-(4-chlorophenyl)-1-cyano-2-methyl-propyl]-amide

HRID 1192384Notes

Reaction equation

HRID 1192384 reaction equation
[C-:1]#[N:2].C([Al+]CC)C.C(O)(C)C.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH3:32])([CH3:31])[CH:20]=[N:21][S@@:22]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)=[O:23])=[CH:15][CH:14]=1>C1(C)C=CC=CC=1.C1COCC1>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH3:32])([CH3:31])[CH:20]([NH:21][S:22]([C:24]2[CH:25]=[CH:26][C:27]([CH3:30])=[CH:28][CH:29]=2)=[O:23])[C:1]#[N:2])=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 16686413Diethyl aluminum cyanideHCID 69790886(R)-4-methylbenzenesulfinic acid [2-(4-chlorophenyl)-2-methylpropyliden]-amide

Product 1

HCID 697909274-Methyl-benzenesulfinic acid[2-(4-chlorophenyl)-1-cyano-2-methyl-propyl]-amideYield 95%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

The diethyl aluminum cyanide (43.5 mL of a 1.0M solution in toluene, 43.5 mmol) was added to isopropanol (28.9 mL, 377 mmol) and stirred at 10° C. for 15 minutes. This solution was cannulated into the (R)-4-methylbenzenesulfinic acid [2-(4-chlorophenyl)-2-methyl-propylidene]-amide (9.28 g, 29.0 mmol) as a solution in 290 mL of THF at −78° C. This solution was allowed to stir for 15 minutes at −78° C. then allowed to warm slowly to room temperature overnight. The solution was quenched with the addition of diluted NaHCO3 solution and extracted with ethyl acetate. The combined organic was washed with brine, separated, dried over Na2SO4, filtered, and concentrated in vacuo to afford the 4-methyl-benzenesulfinic acid [2-(4-chlorophenyl)-1-cyano-2-methyl-propyl]-amide as a colorless oil (9.55 g, 95% yield). The material was heated to 110° C. (reflux) in concentrated HCl solution over the weekend. The solution was cooled to room temperature, washed with ether, then concentrated in vacuo to give the (S)-2-amino-3-(4-chlorophenyl)-3-methyl-butyric acid hydrochloride salt a white solid (1.61 g, 21%). 1H NMR (DMSO-d6, 400 MHz) δ 8.19 (brs, 1H), 7.48 (d, J=8.0 Hz, 2H), 7.41 (d, J=8.0 Hz, 2H), 7.13 (s, 3H), 4.15 (s, 1H), 1.42 (s, 3H), 1.40 (s, 3H). LCMS (APCI+) m/z 228 [M+H]+; Rt=1.81 min.

Workup

  1. stirringto stir for 15 minutes at −78° C.
  2. temperatureto warm slowly to room temperature overnight
  3. customThe solution was quenched with the addition of diluted NaHCO3 solution
  4. extractionextracted with ethyl acetate
  5. washThe combined organic was washed with brine
  6. customseparated
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8a13997a036249b7b2241288f096ca69
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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