Potassium tert-butoxide → 3-Bromo-5-(2,4-dimethoxy-benzyl)-7-oxo-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine-6-carboxylic acid methyl ester

HRID 1465951Notes

Reaction equation

HRID 1465951 reaction equation
C[O:2][C:3]([C:5]1[S:6][CH:7]=[C:8]([Br:28])[C:9]=1[CH2:10][N:11]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=1[O:26][CH3:27])[CH2:12][C:13]([O:15][CH3:16])=[O:14])=O.CC(C)([O-])C.[K+]>C1COCC1>[CH3:16][O:15][C:13]([CH:12]1[N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])[CH2:10][C:9]2[C:8]([Br:28])=[CH:7][S:6][C:5]=2[C:3]1=[O:2])=[O:14]

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 672333554-Bromo-3-{[(2,4-dimethoxy-benzyl)-methoxycarbonylmethyl-amino]-methyl}-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 672336493-Bromo-5-(2,4-dimethoxy-benzyl)-7-oxo-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine-6-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-15 °C

Procedure

4-Bromo-3-{[(2,4-dimethoxy-benzyl)-methoxycarbonylmethyl-amino]-methyl}-thiophene-2-carboxylic acid methyl ester (13.3 g, 28.2 mmol), example 31-c, was dissolved in 277 mL of anhydrous THF and cooled to −15° C. in a brine dry ice bath. A solution of 62.0 mL of 1.0 M potassium tert-butoxide in THF was added slowly to cold solution, and the reaction mixture was stirred at −15° C. for 30 min. and then at room temperature for 2 hours. The reaction was quenched with 62.0 mL of 1N HCl, and 500 mL ammonium chloride, and extracted twice with 600 mL of ethyl acetate. The organic fractions were washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by flash chromatography eluting from silica gel with a gradient of 0-50% ethyl acetate in hexanes to produce 12.4 g of a yellow froth. MS: (+) m/z 461.9, 463.9 (M+Na+, 79Br/81Br).

Workup

  1. waitat room temperature for 2 hours
  2. customThe reaction was quenched with 62.0 mL of 1N HCl, and 500 mL ammonium chloride
  3. extractionextracted twice with 600 mL of ethyl acetate
  4. washThe organic fractions were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography
  8. washeluting from silica gel with a gradient of 0-50% ethyl acetate in hexanes
  9. customto produce 12.4 g of a yellow froth

Sources & evidence

ORD record
ord-424a0d44a7964624b6fa98ea31e443ab
Source dataset
uspto-grants-2015_04
Patent number
US09000006B2

Reaction notes

Loading…