Triethylamine → Ethyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylate

HRID 2243105Notes

Reaction equation

HRID 2243105 reaction equation
[NH2:1][C:2]([CH:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)=[S:3].Br[CH2:18][C:19](=O)[C:20]([O:22][CH2:23][CH3:24])=[O:21].C(N(CC)CC)C>CN(C)C=O>[CH2:23]([O:22][C:20]([C:19]1[N:1]=[C:2]([CH:4]2[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]2)[S:3][CH:18]=1)=[O:21])[CH3:24]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 66144Ethyl bromopyruvateHCID 2735648tert-Butyl 4-carbamothioylpiperidine-1-carboxylate

Product 1

HCID 2795532Ethyl 2-(1-(tert-butoxycarbonyl)piperidin-4-yl)thiazole-4-carboxylateYield 70.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

tert-Butyl 4-(aminocarbothioyl)tetrahydropyridine-1(2H)-carboxylate (May-bridge) (85 mmol; 20.8 g) is dissolved in 250 ml of dimethylformamide and placed at 5° C. Ethyl bromopyruvate (1 eq.; 85 mmol; 16.6 g) dissolved in 50 ml of dimethylformamide is added dropwise. The reaction medium is stirred overnight and excess triethylamine is then added dropwise. The reaction medium is evaporated and the residual brown oil is taken up in ethyl acetate and washed with water (twice) and then with saturated sodium chloride solution (twice). The organic phase is dried over sodium sulfate and evaporated to dryness. The crude product is chromatographed on silica, eluting with dichloromethane to dichloromethane/3% methanol, to give 20.5 g of the expected product in the form of oily crystals. TLC: 1/1 ethyl acetate/hexane: Rf=0.55

Workup

  1. customplaced at 5° C
  2. additionis added dropwise
  3. customThe reaction medium is evaporated
  4. washwashed with water (twice) and then with saturated sodium chloride solution (twice)
  5. dry with materialThe organic phase is dried over sodium sulfate
  6. customevaporated to dryness
  7. customThe crude product is chromatographed on silica
  8. washeluting with dichloromethane to dichloromethane/3% methanol

Sources & evidence

ORD record
ord-98d4b69bae744d53b91d217683d40610
Source dataset
uspto-grants-2010_03
Patent number
US07674803B2

Reaction notes

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