Triethylamine → Methyl 2-(3-(4-(benzyloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate

HRID 75845Notes

Reaction equation

HRID 75845 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:19]=[C:18]([C:20]([OH:22])=O)[O:17][N:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC(OCC(C)C)=O.Cl.[CH3:32][O:33][C:34](=[O:40])[C@H:35]([CH:37]([CH3:39])[CH3:38])[NH2:36].CCN(CC)CC>C1COCC1.CN1CCOCC1>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:19]=[C:18]([C:20]([NH:36][CH:35]([CH:37]([CH3:39])[CH3:38])[C:34]([O:33][CH3:32])=[O:40])=[O:22])[O:17][N:16]=2)=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 111190Methyl valinate hydrochlorideHCID 66572420HCID 66572420, compound

Product 1

HCID 67355429Methyl 2-(3-(4-(benzyloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate

Reagents, catalysts & solvents 2

HCID 79724-MethylmorpholineSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 3-(4-(benzyloxy)phenyl)isoxazole-5-carboxylic acid (300 mg) in THF (10 ml), N-methyl morpholine (0.111 ml) was added and reaction mixture was stirred for 10 minutes at RT. Reaction mixture was cooled to −20° C., isobutyl chloroformate (0.132 ml) was added and stirred for 15-20 minutes at −20 to −30° C. L-valine methyl ester hydrochloride (238 mg) neutralized with Et3N (0.198 ml) in THF (5 ml) and added to the above reaction mixture and stirred at −20 to −30° C. for 5 minutes. Then the reaction mixture was gradually allowed to warm to RT over a period of 1 hour. Solvent was evaporated to obtain pale brown solid, which was purified by column chromatography (silica gel, EtOAc—Chloroform) to obtain off white solid, which was crystallized using EtOAc—petroleum ether to obtain the title compound as white solid. Yield: 232 mg (55%); MS (ES+): m/z 409 (M+1); 1H NMR (DMSO-d6; 300 MHz): δ 9.19 (d, 1H), 7.87 (d, 2H), 7.68 (s, 1H), 7.32-7.49 (m, 5H), 7.19 (d, 2H), 5.19 (s, 2H), 4.31 (m, 1H), 3.67 (s, 3H), 2.22 (m, 1H), 0.96 (d, 6H).

Workup

  1. customreaction mixture
  2. customReaction mixture
  3. temperaturewas cooled to −20° C.
  4. stirringstirred for 15-20 minutes at −20 to −30° C
  5. additionadded to the above reaction mixture
  6. stirringstirred at −20 to −30° C. for 5 minutes
  7. temperatureto warm to RT over a period of 1 hour
  8. customSolvent was evaporated
  9. customto obtain pale brown solid, which
  10. customwas purified by column chromatography (silica gel, EtOAc—Chloroform)
  11. customto obtain off white solid, which
  12. customwas crystallized

Sources & evidence

ORD record
ord-a1bea280ce08496c992a750c8f2eb9fd
Source dataset
uspto-grants-2014_09
Patent number
US08835428B2

Reaction notes

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