Acetic Acid → 4-[2-(3-Methyl-butylamino)-thiazol-4-yl]-benzonitrile

HRID 1191070Notes

Reaction equation

HRID 1191070 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][CH:8]=2)[N:6]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH:29](=O)[CH2:30][CH:31]([CH3:33])[CH3:32].C(O)(=O)C>ClCCCl>[CH3:32][CH:31]([CH3:33])[CH2:30][CH2:29][NH:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:8]=[CH:9][C:10]([C:11]#[N:12])=[CH:13][CH:14]=2)[N:6]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 115523-MethylbutanalHCID 20495894-(2-Amino-1,3-thiazol-4-yl)benzonitrileHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 244317014-[2-(3-Methyl-butylamino)-thiazol-4-yl]-benzonitrileYield 67%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Slurry 4-(2-amino-thiazol-4-yl)-benzonitrile (2.0 g, 9.9 mmol), sodium triacetoxyborohydride (6.3 g, 29.7 mmol), isovaleraldehyde (1.7 g, 19.8 mmol) and acetic acid (3.6 mL) in 1,2-dichloroethane (100 mL) at room temperature under a nitrogen atmosphere. Stir the mixture for 16 h at room temperature. Quench the reaction with saturated aqueous NaHCO3 (75 mL, pH to 7.0-7.5). Extract the mixture twice with DCM (100 mL) and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (40 g) eluting with hexane/EtOAc (20:1 to 3:2 gradient) to obtain the desired intermediate (1.8 g, 67%). MS (ES+) m/z: 272 (M−H)+.

Workup

  1. customat room temperature
  2. customQuench
  3. customthe reaction with saturated aqueous NaHCO3 (75 mL, pH to 7.0-7.5)
  4. extractionExtract the mixture twice with DCM (100 mL)
  5. concentrationconcentrate in vacuo
  6. customPurify the crude mixture by chromatography on silica gel (40 g)
  7. washeluting with hexane/EtOAc (20:1 to 3:2 gradient)

Sources & evidence

ORD record
ord-2d86d64bd9f04150af0a2eb7d083b00e
Source dataset
uspto-grants-2014_03
Patent number
US08680091B2

Reaction notes

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