Butyryl chloride → (1R,2S)-1-(3-chloro-4-cyano-2-methylphenylamino)-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propan-2-yl butyrate

HRID 2388564Notes

Reaction equation

HRID 2388564 reaction equation
[Cl:1][C:2]1[C:9]([CH3:10])=[C:8]([NH:11][C@@H:12]([C:16]2[O:17][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[N:19][N:20]=2)[C@@H:13]([OH:15])[CH3:14])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH3:27][CH2:28][CH2:29][C:30](Cl)=[O:31]>N1C=CC=CC=1.C(Cl)Cl>[C:30]([O:15][C@@H:13]([CH3:14])[C@@H:12]([NH:11][C:8]1[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([Cl:1])[C:9]=1[CH3:10])[C:16]1[O:17][C:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:19][N:20]=1)(=[O:31])[CH2:29][CH2:28][CH3:27]

Participants

5

Reactant 2

HCID 8855Butyryl chlorideHCID 442006592-chloro-4-((1R,2S)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile

Product 1

HCID 67006562(1R,2S)-1-(3-chloro-4-cyano-2-methylphenylamino)-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propan-2-yl butyrateYield 97.5%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-chloro-4-((1R,2S)-2-hydroxy-1-(5-phenyl-1,3,4-oxadiazol-2-yl)propylamino)-3-methylbenzonitrile (200 mg, 0.54 mmol) in pyridine (1.0 mL) and CH2Cl2 (7.0 mL) was added n-butyryl chloride (84 μL, 0.81 mmol). Upon complete addition the reaction mixture was stirred for 60 h, then quenched with 10% aqueous HCl (10 mL). The mixture was partitioned between H2O (25 mL) and CH2Cl2 (30 mL). The aqueous layer was extracted with CH2Cl2 (25 mL). The combined organic extracts were washed with NaHCO3 (30 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide an orange viscous oil, which was purified by flash chromatography over silica gel (15-30% EtOAc in hexanes) to provide the title compound as a colourless solid (231 mg, 97%): 1H NMR (400 MHz, CDCl3, δ in ppm) 7.99 (td, J=1.4, 8.8 Hz, 2H), 7.57-7.47 (m, 3H), 7.38 (d, J=8.6 Hz, 2H), 6.73 (d, J=8.6 Hz, 1H), 5.59 (pentet, J=6.5 Hz, 1H), 5.19 (d, J=8.0 Hz, 1H), 5.03 (dd, J=5.9, 7.8 Hz, 1H), 2.34 (dt, J=2.3, 7.6 Hz, 2H), 2.31 (s, 3H), 1.64 (sextet, J=7.4 Hz, 2H), 1.37 (d, J=6.5 Hz, 3H), 0.92 (t, J=7.4 Hz, 3H).

Workup

  1. additionUpon complete addition the reaction mixture
  2. customquenched with 10% aqueous HCl (10 mL)
  3. customThe mixture was partitioned between H2O (25 mL) and CH2Cl2 (30 mL)
  4. extractionThe aqueous layer was extracted with CH2Cl2 (25 mL)
  5. washThe combined organic extracts were washed with NaHCO3 (30 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide an orange viscous oil, which
  10. customwas purified by flash chromatography over silica gel (15-30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-af4be95483ff472bbcb5bb7d0e3337fa
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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