Hydrogen Bromide → 2-Bromo-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester

HRID 1903684Notes

Reaction equation

HRID 1903684 reaction equation
N[C:2]1[S:3][C:4]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:5]([C:7]([F:10])([F:9])[F:8])[N:6]=1.P(=O)(O)(O)O.[N+]([O-])(O)=O.N([O-])=O.[Na+].[BrH:29]>O>[Br:29][C:2]1[S:3][C:4]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:5]([C:7]([F:10])([F:9])[F:8])[N:6]=1

Participants

7

Reactant 5

HCID 260Hydrogen BromideHCID 944Nitric AcidHCID 1004Phosphoric AcidHCID 676565-Thiazolecarboxylic acid, 2-amino-4-(trifluoromethyl)-, ethyl esterHCID 23668193Sodium Nitrite

Product 1

HCID 132827592-Bromo-4-trifluoromethyl-thiazole-5-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a solution of 4.5 g (0.0187 mole) of ethyl 2-amino-4-trifluoromethyl-5-thiazolecarboxylate in 50 ml. of 85% phosphoric acid at -10° C. was added 25 ml. of nitric acid. To this mixture was added dropwise at -10° C. to -5° C. a solution of 4.0 g (0.0579 mole) of sodium nitrite in 20 ml. of water in 30 minutes. This mixture was stirred for 10 minutes at -10° C. to -5° C. and poured into a solution of 2.70 g (0.0187 mole) of freshly prepared cuprous bromide in 20 ml. of hydrobromic acid. A vigorous evolution of gas occurred. The reaction mixture was stirred for 5 minutes and diluted with water. The solid suspension was filtered and air-dried to give 4.8 g of solid which was chromatographed on silica gel using ether/petroleum ether (1:4) as eluant. The first 1 liter of eluate gave 3.7 g of solid which was recrystallized from petroleum ether to give 2.9 g (51%) of the desired product as white needles, m.p. 75.5°-76.5° C.

Workup

  1. stirringThe reaction mixture was stirred for 5 minutes
  2. filtrationThe solid suspension was filtered
  3. customair-dried

Sources & evidence

ORD record
ord-5856339dd5a04b1e9e3a9587c74d96f4
Source dataset
uspto-grants-1984_03
Patent number
US04437876

Reaction notes

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