Hydrochloric Acid → Ethyl 2-[(2-chloro-1-oxo-3-methylbutyl)-amino]-beta-oxo-alpha-[(2-thiazolylamino)-carbonyl]-3-trifluoromethyl-benzene-propanoate

HRID 1789218Notes

Reaction equation

HRID 1789218 reaction equation
[H-].[Na+].[S:3]1[CH:7]=[CH:6][N:5]=[C:4]1[NH:8][C:9](=[O:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].[Cl:17][CH:18]([C:22]1[O:27][C:26](=[O:28])[C:25]2[CH:29]=[CH:30][CH:31]=[C:32]([C:33]([F:36])([F:35])[F:34])[C:24]=2[N:23]=1)[CH:19]([CH3:21])[CH3:20].Cl>O1CCCC1>[Cl:17][CH:18]([CH:19]([CH3:21])[CH3:20])[C:22]([NH:23][C:24]1[C:32]([C:33]([F:34])([F:35])[F:36])=[CH:31][CH:30]=[CH:29][C:25]=1[C:26](=[O:28])[CH:10]([C:9]([NH:8][C:4]1[S:3][CH:7]=[CH:6][N:5]=1)=[O:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 7339584Ethyl 3-oxo-3-(1,3-thiazol-2-ylamino)propanoateHCID 136556172-(1-chloro-2-methylpropyl)-8-trifluoromethyl-4H-3,1-benzoxazine-4-one

Product 1

HCID 13655618Ethyl 2-[(2-chloro-1-oxo-3-methylbutyl)-amino]-beta-oxo-alpha-[(2-thiazolylamino)-carbonyl]-3-trifluoromethyl-benzene-propanoateYield 72.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Under an inert gas, 5.52 g of sodium hydride dispersed at 55% in oil and 173 ml of tetrahydrofuran were mixed together and then a solution of 26.22 g of ethyl 3-(2-thiazolylamino)-3-oxo-propanoate in 690 ml of tetrahydrofuran was added slowly at 20° C. After stirring for 10 minutes, a solution of 34.5 g of 2-(1-chloro-2-methylpropyl)-8-trifluoromethyl-4H-3,1-benzoxazine-4-one [prepared according to the process described in European Pat. No. 0040573] in 210 ml of tetrahydrofuran was added slowly at 20° C. After stirring at 20° C. for 35 minutes, the mixture was poured into 200 ml of 2N hydrochloric acid and was extracted with ether. The ethereal phase was washed with water, dried and the solvent was evaporated. The residue was triturated in ether and dried to obtain 42.35 g of ethyl 2-[(2-chloro-1-oxo-3-methylbutyl)-amino]-β-oxo-α-[(2-thiazolylamino)-carbonyl]-3-trifluoromethyl-benzene-propanoate melting at 160° C. A second lot of 8.2 g of the said product was obtained afterwards melting at 160° C.

Workup

  1. additionwere mixed together
  2. stirringAfter stirring at 20° C. for 35 minutes
  3. extractionwas extracted with ether
  4. washThe ethereal phase was washed with water
  5. customdried
  6. customthe solvent was evaporated
  7. customThe residue was triturated in ether
  8. customdried

Sources & evidence

ORD record
ord-12b979f700884044918f9eed66626663
Source dataset
uspto-grants-1987_08
Patent number
US04687857

Reaction notes

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