Ethyl formate → HCID 70093552, compound

HRID 1856825Notes

Reaction equation

HRID 1856825 reaction equation
[H-].[Na+].C([O:5][CH2:6][CH3:7])=O.[CH3:8][C:9]1(C)[CH2:26][C:13]2=[C:14]([C:19]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[O:20])[S:15][C:16]([S:17][CH3:18])=[C:12]2[C:11](=[O:27])[CH2:10]1>C1COCC1>[CH3:8][C:9]1([CH3:10])[CH2:26][C:13]2=[C:14]([C:19]([N:21]3[CH2:22][CH2:23][CH2:24][CH2:25]3)=[O:20])[S:15][C:16]([S:17][CH3:18])=[C:12]2[C:11](=[O:27])[C:7]1=[CH:6][OH:5]

Participants

5

Reactant 3

HCID 8025Ethyl formateHCID 24758Sodium hydrideHCID 15407417HCID 15407417, compound

Product 1

HCID 70093552HCID 70093552, compoundYield 52.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (76 mg of a 60% dispension in oil, 1.9 mmol) in THF (5 ml,) was added ethyl formate (0.38 mL, 4.7 mmol) at 0° C. After stirring for 10 min a solution of 6,6-dimethyl-3-methylthio-1-(pyrrolidin-1-ylcarbonyl)-4,5,6,7-tetrahydrobenzo[c]thiophen-4-one (305 mg, 0.94 mmol) in THF (7 mL) was added. The cooling bath was removed and the mixture stirred at room temperature for 18 h. After this time MeOH (0.5 mL) followed by water (0.5 mL) were added and the mixture stirred for 10 min. The solvents were removed in vacuo and the residue dissolved in water. The mixture was acidified to pH1 using 1 M HCl and the resultant solid collected by filtration. The solid was partitioned between EtOAc (20 mL) and water (20 mL). The organic layer was separated, dried (Na2SO4) and evaporated. The residue was chromatographed on silica gel, eluting with EtOAc: DCM (10:90), to give the title compound (173 mg, 52%) as a pale yellow oil. 1H NMR (250 MHz, CDCl3) δ1.18 (6H, s),1.93-1.99 (4H, m), 2.63 (3H, s), 2.82 (2H, s), 3.56-3.70 (4H, m), 7.56 (1H, d, J=10.4 Hz), 14.63 (1H, d J=10.4 Hz).

Workup

  1. additionwas added
  2. customThe cooling bath was removed
  3. additionwere added
  4. stirringthe mixture stirred for 10 min
  5. customThe solvents were removed in vacuo
  6. dissolutionthe residue dissolved in water
  7. filtrationthe resultant solid collected by filtration
  8. customThe solid was partitioned between EtOAc (20 mL) and water (20 mL)
  9. customThe organic layer was separated
  10. dry with materialdried (Na2SO4)
  11. customevaporated
  12. customThe residue was chromatographed on silica gel
  13. washeluting with EtOAc: DCM (10:90)

Sources & evidence

ORD record
ord-614675ce125c41fead6b91349f740ee0
Source dataset
uspto-grants-2000_11
Patent number
US06143773

Reaction notes

Loading…