HCID 59132625, compound → HCID 42603138, compound

HRID 1993027Notes

Reaction equation

HRID 1993027 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][O:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]=[C:18]3[C:23](=[O:24])[O:22]C(C)(C)OC3=O)=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.[C:28]([Mg]Br)#[C:29][CH3:30]>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][O:10][C:11]2[CH:12]=[CH:13][C:14]([CH:17]([C:28]#[C:29][CH3:30])[CH2:18][C:23]([OH:22])=[O:24])=[CH:15][CH:16]=2)=[CH:7][CH:8]=1

Participants

4

Reactant 2

HCID 59132625HCID 59132625, compoundHCID 178419101HCID 178419101, compound

Product 1

HCID 42603138HCID 42603138, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
100 °C

Procedure

To a stirring THF (120 mL) solution of compound 12.2 (13.8 g, 37.5 mmol) under nitrogen was added 1-propynylmagnesium bromide in THF (0.5 N, 97.5 mL) over a period of 20 minutes. After the addition was complete, the reaction mixture was stirred for 20 minutes, quenched with saturated aqueous NH4Cl (50 mL) and extracted with ethyl acetate (3×50 mL). The combined extracts were washed with water, dried over MgSO4, filtered, and concentrated to a brown oil. A solution of this brown oil in 5:1 pyridine-water (360 mL) was heated at 100° C. for 36 h. The reaction mixture was cooled to room temperature and put in an ice-water bath. Concentrated HCl was carefully added to pH ˜2. The resulting suspension was extracted with ethyl acetate (200 mL×3), dried over MgSO4, filtered, and concentrated to an off-white solid. Recrystalization from ethanol gave 9.5 g (78%) of compound 12 as a white powder. 1H NMR (500 MHz) DMSO-d6) δ 12.2 (s, 1H); 7.37 (d, 2H, J=8.5 Hz); 7.27 (d, 2H, J=8.5 Hz); 6.95 (d, 2H, J=8.0 Hz); 6.94 (d, 2H, J=8.5 Hz); 4.99 (s, 2H); 3.95 (m, 1H); 3.76 (s, 3H); 2.60 (m, 2H); 1.78 (d, 3H, J=1.5 Hz). MS ESI (neg.) m/e: 323.0 (M−1).

Workup

  1. additionAfter the addition
  2. customquenched with saturated aqueous NH4Cl (50 mL)
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined extracts were washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to a brown oil
  8. temperatureThe reaction mixture was cooled to room temperature
  9. customput in an ice-water bath
  10. additionConcentrated HCl was carefully added to pH ˜2
  11. extractionThe resulting suspension was extracted with ethyl acetate (200 mL×3)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated to an off-white solid
  15. customRecrystalization from ethanol

Sources & evidence

ORD record
ord-a3423aebbe4e42a49406b27cd04bd0da
Source dataset
uspto-grants-2010_01
Patent number
US07649110B2

Reaction notes

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