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

HRID 415191Notes

Reaction equation

HRID 415191 reaction equation
[F: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>[F: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 59626030HCID 59626030, compound

Product 1

HCID 666213482-(4-Fluorophenyl)benzo[d]oxazole-4-carboxamideYield 7.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

2-(4-fluorophenyl)benzo[d]oxazole-4-carboxylic acid (0.064 g, 0.25 mmol) in dimethyl formamide (10 mL) was added HOBT (0.043 g, 0.28 mmol), EDCI (0.058 g, 0.3 mmol), DIPEA (0.097 g, 0.75 mmol) and ammonium chloride (0.0133 g, 0.25 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 0.005 g 2-(4-fluorophenyl)benzo[d]oxazole-4-carboxamide as a solid (yield: 7.8%). 1H-NMR (400 MHz, DMSO-d6) δ 7.37-7.40 (m, 1H), 7.46-7.56 (m, 3H), 7.97-8.05 (m, 3H), 8.38 (s, 2H); LC-MS (ESI) m/z 257 [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-c51268ed86524dc6b863fc450abf48b2
Source dataset
uspto-grants-2012_01
Patent number
US08088760B2

Reaction notes

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