Hydrochloric Acid → HCID 18189440, compound

HRID 1358129Notes

Reaction equation

HRID 1358129 reaction equation
[OH:1][C:2]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([CH2:16][S:17]([NH2:20])(=[O:19])=[O:18])=[CH:15][C:9]=3[CH:8]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.C[Si]([CH:31]([Si](C)(C)C)[C:32](N)=O)(C)C.CC(C)([O-])C.[K+].C(I)C.Cl.C([O-])(O)=O.[Na+]>C1COCC1>[CH2:31]([O:1][C:2]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([CH2:16][S:17]([NH2:20])(=[O:19])=[O:18])=[CH:15][C:9]=3[CH:8]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[O:7][C:6]=2[CH:5]=[CH:4][CH:3]=1)[CH3:32]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6340IodoethaneHCID 516892Sodium BicarbonateHCID 11708267BistrimethylsilylacetamidHCID 18188598HCID 18188598, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 18189440HCID 18189440, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of Example 35F (77 mg, 0.210 mmol) in THF (5 mL) at 0° C. was treated with bistrimethylsilylacetamide (52 μL, 0.210 mmol), stirred for 1 hour, and concentrated. The concentrate was dissolved in THF (5 mL), cooled to 0° C., treated with 1M potassium tert-butoxide (210 μL, 0.210 mmol), stirred for 1 hour, treated with ethyl iodide (17 μL, 0.210 mmol), stirred at room temperature for 72 hours, treated with 1M HCl (5 mL), stirred for 2 hours, poured into saturated NaHCO3, and extracted with ethyl acetate. The extract was washed with brine, dried (Na2SO4), filtered, and concentrated. The concentrate was purified by reverse-phase HPLC with CH3CN/water to provide the desired product as the fraction which eluted at 25 minutes. MS (ESI(−)Q1MS) m/z 394 (M−H)−; 1H NMR (400 MHz, DMSO-d6) δ 9.84 (br s, 1H), 8.43-8.41 (d, J=8.7 Hz, 1H), 7.37-7.23 (m, 6H), 7.14-7.10 (t, J=8.0 Hz, 1H), 6.89 (d, J=2.4 Hz, 1H), 6.71-6.69 (dd, J=7.6, 0.7 Hz, 1H), 6.63-6.60 (dd, J=7.3, 1.0 Hz, 1H), 6.20 (s, 1H), 4.16-4.09 (m, 2H), 3.00 (s, 3H), 1.46-1.42 (t, J=6.9, 3H).

Workup

  1. concentrationconcentrated
  2. dissolutionThe concentrate was dissolved in THF (5 mL)
  3. stirringstirred for 1 hour
  4. stirringstirred at room temperature for 72 hours
  5. stirringstirred for 2 hours
  6. extractionextracted with ethyl acetate
  7. washThe extract was washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe concentrate was purified by reverse-phase HPLC with CH3CN/water

Sources & evidence

ORD record
ord-03e4d1b1260d4032826d43a66f239a3d
Source dataset
uspto-grants-2003_07
Patent number
US06593480B2

Reaction notes

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