Potassium Carbonate → 2-t-Butoxycarbonylamino-4-ethynyl-thiophene-3-carboxylic acid ethyl ester

HRID 1244160Notes

Reaction equation

HRID 1244160 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([CH:11]=O)=[CH:9][S:8][C:7]=1[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:5])[CH3:2].[C:21](=O)([O-])[O-].[K+].[K+].COP(C(=[N+]=[N-])C(=O)C)(=O)OC>CCO>[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:11]#[CH:21])=[CH:9][S:8][C:7]=1[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 86596546HCID 86596546, compoundHCID 136023029(1E)-1-diazo-1-dimethoxyphosphorylpropan-2-one

Product 1

HCID 865965472-t-Butoxycarbonylamino-4-ethynyl-thiophene-3-carboxylic acid ethyl esterYield 93.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-t-Butoxycarbonylamino-4-formyl-thiophene-3-carboxylic acid ethyl ester (6.35 g, 21.31 mmol) from example 240d was dissolved in absolute EtOH (325 mL). This was treated with potassium carbonate (%.89 g, 42.62 mmol) followed by (1-diazo-2-oxopropyl)-phosphonic acid dimethyl ester (4.91 g, 25.57 mmol). The reaction was stirred at room temperature for 14 hr. The reaction was concentrated to 12 volume then poured into sat. NaHCO3 (250 mL) and then extracted with EtOAc (3×250 mL). The combined extracts were washed with brine (2×250 mL). They were dried (Na2SO4), filtered and the solvent removed in vacuo. The crude product was purified by flash chromatography (SiO2, 1 EtOAc/9 hexanes) to afford the title compound (5.86 g, 93%). MS m/e (CI) 296.0 (M+H), 313.1 (M+NH4); 1H NMR (300 MHz, CDCl3): δ ppm 1.41 (t, 3H), 1.53 (s, 9H), 3.11 (s, 1H), 4.37 (q, 2H), 6.98 (s, 1H), 10.30 (s, 1H).

Workup

  1. concentrationThe reaction was concentrated to 12 volume
  2. additionthen poured into sat. NaHCO3 (250 mL)
  3. extractionextracted with EtOAc (3×250 mL)
  4. washThe combined extracts were washed with brine (2×250 mL)
  5. dry with materialThey were dried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe crude product was purified by flash chromatography (SiO2, 1 EtOAc/9 hexanes)

Sources & evidence

ORD record
ord-3c097bc778484801af3d008c07685cc9
Source dataset
uspto-grants-2006_10
Patent number
US07119205B2

Reaction notes

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