Methyl 2-amino-5-(propan-2-yl)-1,3-thiazole-4-carboxylate → Methyl 5-isopropylthiazole-4-carboxylate

HRID 244667Notes

Reaction equation

HRID 244667 reaction equation
N[C:2]1[S:3][C:4]([CH:11]([CH3:13])[CH3:12])=[C:5]([C:7]([O:9][CH3:10])=[O:8])[N:6]=1.N([O-])=O.[Na+]>OP=O>[CH3:13][CH:11]([C:4]1[S:3][CH:2]=[N:6][C:5]=1[C:7]([O:9][CH3:10])=[O:8])[CH3:12]

Participants

4

Reactant 2

HCID 737584Methyl 2-amino-5-(propan-2-yl)-1,3-thiazole-4-carboxylateHCID 23668193Sodium Nitrite

Product 1

HCID 13015587Methyl 5-isopropylthiazole-4-carboxylateYield 95.5%

Reagents, catalysts & solvents 1

HCID 22497phosphenous acidSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of methyl 2-amino-5-(1-methylethyl)-1,3-thiazole-4-carboxylate (2.15 g) (available from ABCR) in 30% hypophosphorus acid (53 ml) at −5° C. was added, slowly beneath the surface, maintaining the temperature between −5 and 0° C., sodium nitrite (1.6 g) and the mixture was stirred for a further 1 h at 0° C. The cooling bath was removed for 2 h, then replaced while a cool solution of sodium hydroxide (8.5 g) in water (100 ml) added slowly. The solution was neutralised by the addition of solid sodium hydrogencarbonate and extracted with diethyl ether (50 ml), then dried over sodium sulphate. The mixture was evaporated and purified by chromatography on silica gel eluting with a gradient of ethyl acetate in cyclohexane to give the title compound (1.9 g) as a yellow oil.

Workup

  1. customThe cooling bath was removed for 2 h
  2. additionadded slowly
  3. additionThe solution was neutralised by the addition of solid sodium hydrogencarbonate
  4. extractionextracted with diethyl ether (50 ml)
  5. dry with materialdried over sodium sulphate
  6. customThe mixture was evaporated
  7. custompurified by chromatography on silica gel eluting with a gradient of ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-d6570c87c80f48d29033f456e686f49e
Source dataset
uspto-grants-2014_02
Patent number
US08658635B2

Reaction notes

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