Acetic Acid → HCID 135475794, compound

HRID 2110609Notes

Reaction equation

HRID 2110609 reaction equation
[NH2:1][C@@:2]1([CH2:34][CH2:35][CH:36]([CH3:38])[CH3:37])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[C:4]([C:13]2[NH:18][C:17]3[CH:19]=[CH:20][C:21]([NH:23]C(=O)OC(C)(C)C)=[CH:22][C:16]=3[S:15](=[O:32])(=[O:31])[N:14]=2)[C:3]1=[O:33].[CH:39](=O)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].N1C=CC=CC=1.[CH3:76][S:77](Cl)(=[O:79])=[O:78]>ClCCl.O>[CH2:39]([NH:1][C@@:2]1([CH2:34][CH2:35][CH:36]([CH3:37])[CH3:38])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([OH:12])=[C:4]([C:13]2[NH:18][C:17]3[CH:19]=[CH:20][C:21]([NH:23][S:77]([CH3:76])(=[O:79])=[O:78])=[CH:22][C:16]=3[S:15](=[O:32])(=[O:31])[N:14]=2)[C:3]1=[O:33])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 136396995HCID 136396995, compound

Product 1

HCID 135475794HCID 135475794, compoundYield 68.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of Example 83B (100 mg, 0.18 mmol) in dichloromethane (2.5 mL) was added benzaldehyde (23 μL, 0.22 mmol), acetic acid (26 μL, 0.46 mmol) and sodium triacetoxyborohydride (63 mg, 0.30 mmol) and the solution was stirred at room temperature for 16 hours. 10% NaHCO3 (10 mL) was added and the solution stirred for 10 minutes, diluted with H2O (10 mL) and the solution extracted with dichloromethane (3×10 mL). The organic extracts were combined, dried (Na2SO4), the drying agent filtered off and the solvent removed in vacuo to give a crude residue which was purified by column chromatography on silica gel (2% methanol/chloroform). The pure material was dissolved in 4M HCl in dioxane (4 mL) and the solution stirred at room temperature for 3 hours, solvent removed in vacuo and the residue dissolved in dichloromethane (4 mL). To this solution was added pyridine (56 uL, 0.9 mmol) and methanesulfonyl chloride (13 μL, 0.22 mmol) and the solution stirred at room temperature for 48 hours, solvent was removed in vacuo and the crude residue was purified by column chromatography on silica gel 4-6% methanol/chloroform) to give the title compound as a colorless solid (75 mg, 67%); 1H NMR (d6-DMSO) δ 14.00 (s, 1H), 9.98 (s, 1H), 8.21, 8.19 (d, 1H), 7.94, 7.92 (d, 1H), 7.77-7.27 (m, 10H), 3.02 (s, 3H), 2.35-2.17 (m, 1H), 2.05-1.89 (m, 1H), 1.36-1.21 (m, 1H), 0.73-0.61 (q, 6H), 0.58-0.45 (m, 1H); MS (ESI) m/z 609 (M+H+).

Workup

  1. stirringthe solution stirred for 10 minutes
  2. extractionthe solution extracted with dichloromethane (3×10 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationthe drying agent filtered off
  5. customthe solvent removed in vacuo
  6. customto give a crude residue which
  7. customwas purified by column chromatography on silica gel (2% methanol/chloroform)
  8. dissolutionThe pure material was dissolved in 4M HCl in dioxane (4 mL)
  9. stirringthe solution stirred at room temperature for 3 hours
  10. customsolvent removed in vacuo
  11. dissolutionthe residue dissolved in dichloromethane (4 mL)
  12. stirringthe solution stirred at room temperature for 48 hours
  13. customsolvent was removed in vacuo
  14. customthe crude residue was purified by column chromatography on silica gel 4-6% methanol/chloroform)

Sources & evidence

ORD record
ord-b062d487fa7a44d0a160d0fd89d3bf2f
Source dataset
uspto-grants-2009_04
Patent number
US07517876B2

Reaction notes

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