Ethyl chloroformate → HCID 67276125, compound

HRID 1697868Notes

Reaction equation

HRID 1697868 reaction equation
C([O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([C:15]([OH:17])=O)=[CH:10][CH:9]=[CH:8]2)(=O)C.CCN(C(C)C)C(C)C.ClC(OCC)=O.[NH2:33][C:34]1[CH:38]=[C:37]([CH3:39])[O:36][N:35]=1>C1COCC1.CCOC(C)=O.O>[OH:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([C:15]([NH:33][C:34]1[CH:38]=[C:37]([CH3:39])[O:36][N:35]=1)=[O:17])=[CH:10][CH:9]=[CH:8]2

Participants

7

Reactant 4

HCID 10928Ethyl chloroformateHCID 661723-Amino-5-methylisoxazoleHCID 81531Diisopropylethylamine2×HCID 19925747HCID 19925747, compound

Product 1

HCID 67276125HCID 67276125, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 22728543Water ethylacetateSolvent

Conditions

Temperature
0 °C

Procedure

6-Acetoxy-1-naphthoic acid (200 mg, from Example 1) was mixed with DIPEA (1.2 eq) in THF and stirred at 0° C. for 10 minutes, to the reaction was added ethyl chloroformate (1 eq) slowly and further stirred for 1.5 hours from 0° C. to RT. To the reaction was added DIPEA (1.2 eq) and 3-amino-5-methylisoxazole (1.2 eq), the reaction was stirred at RT for 12 hours and mixed with EtOAc/H2O, further extracted with EtOAc and dried. The solution was evaporated and mixed with 15% KOH (2 ml) in MeOH (10 ml) further stirred at RT for 30 minutes. The solvent was evaporated and the residue was adjusted to weak acidic with 2N HCl, the solid was filtered and washed with water twice and cold MeOH to give 6-Hydroxy-N-(5-methylisoxazol-3-yl)-1-naphthamide (90 mg).

Workup

  1. stirringfurther stirred for 1.5 hours from 0° C. to RT
  2. stirringthe reaction was stirred at RT for 12 hours
  3. extractionfurther extracted with EtOAc
  4. customdried
  5. customThe solution was evaporated
  6. additionmixed with 15% KOH (2 ml) in MeOH (10 ml)
  7. stirringfurther stirred at RT for 30 minutes
  8. customThe solvent was evaporated
  9. filtrationthe solid was filtered
  10. washwashed with water twice

Sources & evidence

ORD record
ord-589b6404539a4908baaad09f2c1fe8ee
Source dataset
uspto-grants-2012_04
Patent number
US08163923B2

Reaction notes

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