Potassium tert-butoxide → 5-(2,4-Dimethoxy-benzyl)-7-oxo-2-phenyl-4,5,6,7-tetrahydro-thiazolo[4,5-c]pyridine-6-carboxylic acid ethyl ester

HRID 642278Notes

Reaction equation

HRID 642278 reaction equation
C([O:3][C:4]([C:6]1[S:10][C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[N:8][C:7]=1[CH2:17][N:18]([CH2:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][C:27]=1[O:34][CH3:35])[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=O)C.CC(C)([O-])C.[K+]>C1COCC1>[CH2:23]([O:22][C:20]([CH:19]1[N:18]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][C:27]=2[O:34][CH3:35])[CH2:17][C:7]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[S:10][C:6]=2[C:4]1=[O:3])=[O:21])[CH3:24]

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 684272284-{[(2,4-Dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-2-phenyl-thiazole-5-carboxylic acid ethyl ester

Product 1

HCID 684267715-(2,4-Dimethoxy-benzyl)-7-oxo-2-phenyl-4,5,6,7-tetrahydro-thiazolo[4,5-c]pyridine-6-carboxylic acid ethyl esterYield 102.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A yellow solution of 4-{[(2,4-dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-2-phenyl-thiazole-5-carboxylic acid ethyl ester (5.60 g, 0.01 mol) in THF (45 mL) was added 1 M potassium tert-butoxide (KOtBu) in THF (24.7 mL, 0.02 mmol) at −78° C., a dark red suspension quickly appeared. The mixture was stirred at −78° C. for 20 min, warmed to room temperature and stirred at that temperature for 2 h before it was quenched with aqueous ammonium chloride, extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give 5-(2,4-dimethoxy-benzyl)-7-oxo-2-phenyl-4,5,6,7-tetrahydro-thiazolo[4,5-c]pyridine-6-carboxylic acid ethyl ester as a yellow oil (4.63 g). It was dissolved in dichloromethane (40 mL) and thionyl chloride (1.12 mL, 0.02 mmol) was added drop wise. The mixture was stirred at room temperature for 3.5 h before it was quenched with saturated sodium bicarbonate, extracted with dichloromethane. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with a gradient of ethyl acetate and dichloromethane to give the title compound as a yellow solid (2.74 g): 1H NMR (CDCl3, 200 MHz): δ=11.52 (s, 1H), 9.00 (s, 1H), 8.13 (m, 2H), 7.55 (m, 3H), 4.58 (q, J=7.0 Hz, 2H), 1.53 (t, J=7.0 Hz, 3H); MS: (+) m/z 301.0 (M+1).

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred at that temperature for 2 h before it
  3. customwas quenched with aqueous ammonium chloride
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-77f2c20a004a40cc86af8509da305020
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

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