Butyryl chloride → HCID 44199835, compound

HRID 2388528Notes

Reaction equation

HRID 2388528 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][C:24]([F:27])=[C:23]([OH:28])[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].[CH3:29][CH2:30][CH2:31][C:32](Cl)=[O:33]>N1C=CC=CC=1.C(Cl)Cl>[C:32]([O:28][C:23]1[CH:22]=[C:21]([C:18]2[O:17][C:16]([C@H:12]([NH:11][C:8]3[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([Cl:1])[C:9]=3[CH3:10])[C@H:13]([O:15][C:16](=[O:17])[CH2:12][CH2:13][CH3:14])[CH3:14])=[N:20][N:19]=2)[CH:26]=[CH:25][C:24]=1[F:27])(=[O:33])[CH2:31][CH2:30][CH3:29]

Participants

5

Reactant 2

HCID 8855Butyryl chlorideHCID 44201237HCID 44201237, compound

Product 1

HCID 44199835HCID 44199835, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-chloro-4-((1R,2R)-1-(5-(4-fluoro-3-hydroxyphenyl)-1,3,4-oxadiazol-2-yl)-2-hydroxypropylamino)-3-methylbenzonitrile (Example 41) (135.5 mg, 0.34 mmol) in pyridine (0.6 mL) and CH2Cl2 (4 mL) was added n-butyryl chloride (0.17 mL, 1.68 mmol). Upon complete addition the reaction mixture was stirred for 23 h, then quenched with 10% aqueous HCl (6 mL). The mixture was partitioned between H2O (40 mL) and CH2Cl2 (40 mL). The aqueous layer was extracted with CH2Cl2 (40 mL). The combined organic extracts were washed with NaHCO3 (45 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a yellow oil, which was purified by flash chromatography over silica gel (20-25% EtOAc in hexanes) to provide the title compound as an off white solid (137.3 mg, 74%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 7.94 (ddd, J=2.2, 4.5, 8.6 Hz, 1H), 7.86 (dd, J=2.0, 7.0 Hz, 1H), 7.52 (d, J=8.6 Hz, 1H), 7.52 (dd, J=8.8, 10.0 Hz, 1H), 6.95 (d, J=8.8 Hz, 1H), 6.13 (d, J=8.8 Hz, 1H), 5.68 (pentet, J=6.5 Hz, 1H), 5.36 (dd, J=6.5, 8.4 Hz, 1H), 2.67 (t, J=7.2 Hz, 2H), 2.28-2.22 (m, 2H), 2.07-2.03 (m, 2H), 1.82-1.71 (m, 2H), 1.53 (d, J=6.5 Hz, 3H), 1.03 (t, J=7.2 Hz, 3H), 0.82 (t, J=7.4 Hz, 3H).

Workup

  1. additionUpon complete addition the reaction mixture
  2. customquenched with 10% aqueous HCl (6 mL)
  3. customThe mixture was partitioned between H2O (40 mL) and CH2Cl2 (40 mL)
  4. extractionThe aqueous layer was extracted with CH2Cl2 (40 mL)
  5. washThe combined organic extracts were washed with NaHCO3 (45 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto provide a yellow oil, which
  10. customwas purified by flash chromatography over silica gel (20-25% EtOAc in hexanes)

Sources & evidence

ORD record
ord-4aa82bf35d374fd89fa61daecc942c65
Source dataset
uspto-grants-2012_09
Patent number
US08268872B2

Reaction notes

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