Methanol → HCID 25234699, compound

HRID 876123Notes

Reaction equation

HRID 876123 reaction equation
[C:1]([C:5]1[C:6]([O:34][CH3:35])=[C:7]([CH:23]=[C:24]([N:26]2[CH:31]=[CH:30][C:29](=[O:32])[NH:28][C:27]2=[O:33])[CH:25]=1)/[CH:8]=[CH:9]/[C:10]1[CH:15]=[CH:14][C:13]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])=[CH:12][C:11]=1[CH2:21][OH:22])([CH3:4])([CH3:3])[CH3:2].S(Cl)(Cl)=O.[CH3:40][O-].[Na+].CO>C(Cl)Cl>[C:1]([C:5]1[C:6]([O:34][CH3:35])=[C:7]([CH:23]=[C:24]([N:26]2[CH:31]=[CH:30][C:29](=[O:32])[NH:28][C:27]2=[O:33])[CH:25]=1)/[CH:8]=[CH:9]/[C:10]1[CH:15]=[CH:14][C:13]([NH:16][S:17]([CH3:20])(=[O:18])=[O:19])=[CH:12][C:11]=1[CH2:21][O:22][CH3:40])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 10942334Sodium MethoxideHCID 25234700HCID 25234700, compound

Product 1

HCID 25234699HCID 25234699, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Example 28 (32 mg, 0.064 mmol) in anhydrous CH2Cl2 (1 ml) was added thionyl chloride (23 μL, 0.32 mmol), and the resulting mixture was stirred at room temperature for 30 min. The mixture was partitioned between saturated aq. NaHCO3 (5 ml) and CH2Cl2 (5 ml) and the organic layer was dried over Na2SO4, filtered and concentrated. The residue was dissolved in MeOH (1 ml), and a solution of 25% NaOMe in MeOH (584, 0.254 mmol) was added. The resulting mixture was stirred at 50° C. for 2 h. The mixture was partitioned between 1 N aq. HCl (10 ml) and EtOAc (2×10 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using 3% MeOH in CH2Cl2 as the eluent to give the title compound (15 mg, 46%). 1H NMR (300 MHz, DMSO-d6) δ 11.43 (s, 1H) 9.86 (s, 1H) 7.62-7.87 (m, 3H) 7.12-7.39 (m, 5H) 5.66 (d, J=1.72 Hz, 1H) 4.58 (s, 2H) 3.78 (s, 3H) 3.35 (s, 3H) 3.00 (s, 3H) 1.38 (s, 9H).

Workup

  1. customThe mixture was partitioned between saturated aq. NaHCO3 (5 ml) and CH2Cl2 (5 ml)
  2. dry with materialthe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in MeOH (1 ml)
  6. stirringThe resulting mixture was stirred at 50° C. for 2 h
  7. customThe mixture was partitioned between 1 N aq. HCl (10 ml) and EtOAc (2×10 ml)
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography on silica gel using 3% MeOH in CH2Cl2 as the eluent

Sources & evidence

ORD record
ord-251d84dc7b2e4c1cbad947873e06258a
Source dataset
uspto-grants-2015_03
Patent number
US08986740B2

Reaction notes

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