Sodium Hydroxide → HCID 60083753, compound

HRID 434061Notes

Reaction equation

HRID 434061 reaction equation
CO[C:3]([C:5]1[N:6]=[CH:7][O:8][C:9]=1[C:10]1[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=1[Cl:17])=[O:4].[OH-].[Na+].[NH2:20][C:21]1[CH:22]=[C:23]([CH2:27][C:28]([NH:30][C:31]2[CH:36]=[C:35]([O:37][CH3:38])[C:34]([O:39][CH3:40])=[C:33]([O:41][CH3:42])[CH:32]=2)=[O:29])[CH:24]=[CH:25][CH:26]=1.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.C(Cl)Cl.O.C1COCC1.CO>[CH3:38][O:37][C:35]1[CH:36]=[C:31]([NH:30][C:28](=[O:29])[CH2:27][C:23]2[CH:24]=[CH:25][CH:26]=[C:21]([NH:20][C:3]([C:5]3[N:6]=[CH:7][O:8][C:9]=3[C:10]3[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=3[Cl:17])=[O:4])[CH:22]=2)[CH:32]=[C:33]([O:41][CH3:42])[C:34]=1[O:39][CH3:40]

Participants

10

Reactant 4

HCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 187562514-Methoxycarbonyl-5-(2-chloro-6-fluorophenyl)oxazoleHCID 187562602-(3-aminophenyl)-N-(3,4,5-trimethoxyphenyl)acetamide

Product 1

HCID 60083753HCID 60083753, compoundYield 39%

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4-methoxycarbonyl-5-(2-chloro-6-fluorophenyl)oxazole (236 mg, 0.927 mmol), MeOH (5 ml), THF (1 ml), and 2N NaOH (1.5 ml, 3.00 mmol) was heated to 50° C. for 30 minutes. The mixture was cooled to room temperature and H2O and ice were added followed by acidification to pH 2 and extraction with EtOAc. The organic fraction was washed (brine), dried (Na2SO4), filtered, and concentrated to give the crude carboxylic acid. The crude carboxylic acid, 2-(3-aminophenyl)-N-(3,4,5-trimethoxyphenyl)acetamide (292 mg, 0.927 mmol), EDCI (354 mg, 1.85 mmol), and DMAP (11 mg, 0.093 mmol) were allowed to react in CH2Cl2 (5 ml) for 15 h at room temperature under N2. The mixture was applied directly to a silica gel column and elution with hexanes/EtOAc (gradient) gave the title compound (193 mg, 39%).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionfollowed by acidification to pH 2 and extraction with EtOAc
  3. washThe organic fraction was washed (brine)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give the crude carboxylic acid
  8. washThe mixture was applied directly to a silica gel column and elution with hexanes/EtOAc (gradient)

Sources & evidence

ORD record
ord-2419ff12db864a929ec6f66ae00feeb4
Source dataset
uspto-grants-2003_12
Patent number
US06670373B1

Reaction notes

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