Hydrochloric Acid → 2-(4-Chlorophenyl)benzo[d]oxazole-4-carboxamide

HRID 415193Notes

Reaction equation

HRID 415193 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:11](=[C:13]([C:17]([OH:19])=O)[CH:14]=[CH:15][CH:16]=3)[N:12]=2)=[CH:4][CH:3]=1.C1C=CC2N(O)N=[N:26]C=2C=1.CCN=C=NCCCN(C)C.CCN(C(C)C)C(C)C.[Cl-].[NH4+].Cl>CN(C)C=O.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[C:11](=[C:13]([C:17]([NH2:26])=[O:19])[CH:14]=[CH:15][CH:16]=3)[N:12]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 596258542-(4-Chlorophenyl)benzoxazole-4-carboxylic acid

Product 1

HCID 666213472-(4-Chlorophenyl)benzo[d]oxazole-4-carboxamideYield 14.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-(4-chlorophenyl)benzo[d]oxazole-4-carboxylic acid 4 (0.137 g, 0.5 mmol) in dimethyl formamide (10 mL) was added was added HOBT (0.085 g, 0.55 mmol), EDCI (0.115 g, 0.6 mmol), DIPEA (0.194 g, 1.5 mmol) and ammonium chloride (0.0265 g, 0.5 mmol). The reaction mixture was stirred at room temperature for 20 hr, cooled and poured into water (10 mL). The solution was acidified to pH=3 with 1N aqueous hydrochloric acid. Then the solution was extracted with dichloromethane (70 mL×3). The organic layer was washed with brine, dried over anhydrous sodium sulfate, condensed in vacuum and separated by silica gel chromatography (ethyl acetate:methanol=1:0 to 10:1) to afford 10 mg 2-(4-chlorophenyl)benzo[d]oxazole-4-carboxamide (yield: 14.8%). 1H-NMR (400 MHz, DMSO-d6) δ 7.54-7.58 (t, J=8.0 Hz, 1H), 7.70-7.72 (d, J=8.0 Hz, 2H), 7.96-8.02 (m, 3H), 8.31-8.33 (d, J=8.0 Hz, 2H), 8.44 (s, 1H); LC-MS (ESI) m/z 273 [M+1]+.

Workup

  1. temperaturecooled
  2. extractionThen the solution was extracted with dichloromethane (70 mL×3)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate, condensed in vacuum
  5. customseparated by silica gel chromatography (ethyl acetate:methanol=1:0 to 10:1)

Sources & evidence

ORD record
ord-89d7dcfccc144392aeca76254b95a5e2
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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