Bromine → Ethyl 2-methyl-4,5,6,7-tetrahydrobenzo[d]thiazole-4-carboxylate

HRID 243662

Reaction equation

HRID 243662 reaction equation
O=[C:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[C:8]([O:10][CH2:11][CH3:12])=[O:9].BrBr.[C:15]([NH2:18])(=[S:17])[CH3:16]>C(OCC)C.CCOC(C)=O>[CH3:16][C:15]1[S:17][C:7]2[CH2:6][CH2:5][CH2:4][CH:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:2]=2[N:18]=1

Participants

6

Reactant 3

HCID 24408BromineHCID 95543Ethyl 2-oxocyclohexanecarboxylateHCID 2723949Thioacetamide

Product 1

HCID 12917740Ethyl 2-methyl-4,5,6,7-tetrahydrobenzo[d]thiazole-4-carboxylateYield 31%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 2-oxocyclohexanecarboxylate (15 g, 88 mmol) in anhydrous diethyl ether (40 mL) cooled at 0° C. was added bromine (4.5 mL, 88 mmol) dropwise over 15 mins. After complete addition mixture allowed to warm to room temp over 90 min. Mixture diluted with EtOAc (100 mL) and washed with sat. NaHCO3, sat. NaCl, dried over MgSO4, filtered and evaporated. Residue taken up in ethanol (100 mL) and thioacetamide (6.6 g, 88 mmol) added. Mixture stirred at room temp for 1 h then at reflux overnight. Mixture evaporated and residue partitioned between sat. NaHCO3 and DCM. Organic layer dried over MgSO4, filtered and evaporated. Residue purified by MPLC (Biotage Horizon: FLASH 65i) eluent: 100% Hexanes (500 mL), gradient 0 to 25% EtOAc in Hexanes (1200 mL) then 25% EtOAc in Hexanes (1200 mL) to give the title compound (6.14 g, 31%) as a pale orange oil. 1HNMR (500 MHz, CDCl3) δ: 4.22 (q, J=7.1, 2H), 3.84 (t, J=5.5, 1H), 2.80 (m, 1H), 2.73 (m, 1H), 2.65 (s, 3H), 2.18 (m, 1H), 2.11-1.95 (m, 2H), 1.85 (m, 1H), 1.29 (t, J=7.1, 3H).

Workup

  1. washwashed with sat. NaHCO3, sat. NaCl
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. temperatureat reflux overnight
  6. customMixture evaporated
  7. customresidue partitioned between sat. NaHCO3 and DCM
  8. dry with materialOrganic layer dried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customResidue purified by MPLC (Biotage Horizon: FLASH 65i) eluent

Sources & evidence

ORD record
ord-59713acd124047149a2bef5418c0c070
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Linked notes

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