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

HRID 1888147

反応式

HRID 1888147 の反応式
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.C(OCC)(=O)C>[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

参加物

6

反応物 3

HCID 24408BromineHCID 95543Ethyl 2-oxocyclohexanecarboxylateHCID 2723949Thioacetamide

生成物 1

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

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 15 g (88 mmol) of ethyl 2-oxocyclohexanecarboxylate in 40 mL of anhydrous diethyl ether cooled to 0° C. was added 4.5 mL (88 mmol) of bromine dropwise over 15 min. After complete addition the mixture was allowed to warm to ambient temperature over 90 min. The mixture was next diluted with 100 mL of ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution, brine, dried over magnesium sulfate, filtered and evaporated in vacuo. The residue was taken up in 100 mL of ethanol and 6.6 g (88 mmol) of thioacetamide was added. The mixture was stirred at ambient temperature for 1 h, then at reflux overnight. After evaporation of all volatiles in vacuo the residue was partitioned between a saturated aqueous sodium bicarbonate solution and dichloromethane. The layers were separated and the organic phase was dried over magnesium sulfate and evaporated in vacuo. The crude residue was 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 as a pale orange oil. 1H NMR (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).

後処理

  1. additionAfter complete addition the mixture
  2. washwashed with a saturated aqueous sodium bicarbonate solution, brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. temperatureat reflux overnight
  7. customAfter evaporation of all volatiles in vacuo the residue
  8. customwas partitioned between a saturated aqueous sodium bicarbonate solution and dichloromethane
  9. customThe layers were separated
  10. dry with materialthe organic phase was dried over magnesium sulfate
  11. customevaporated in vacuo
  12. customThe crude residue was purified by MPLC (Biotage Horizon: FLASH 65i) eluent

出典と根拠

ORDレコード
ord-2888f53ba4ab4d1483099fa8d96b7ef3
出典データセット
uspto-grants-2013_08
特許番号
US08501786B2

関連ノート

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