Acetic Acid → HCID 25127070, compound

HRID 2093728Notes

Reaction equation

HRID 2093728 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:11]([N:25]2[CH2:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][C:31]=3[N:34]3[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)[C:26]2=[O:40])[CH2:12][CH2:13][CH2:14][N:15]([CH3:24])[S:16]([C:19]2[S:20][CH:21]=[CH:22][CH:23]=2)(=[O:18])=[O:17])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C(O)(=O)C.C(O[C:48]1(O[Si](C)(C)C)[CH2:50][CH2:49]1)C.C([BH3-])#N.[Na+]>CO>[CH:48]1([N:37]2[CH2:36][CH2:35][N:34]([C:31]3[CH:30]=[CH:29][CH:28]=[C:27]4[C:32]=3[CH2:33][N:25]([C@@H:11]([C:5]3[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:12][CH2:13][CH2:14][N:15]([CH3:24])[S:16]([C:19]3[S:20][CH:21]=[CH:22][CH:23]=3)(=[O:18])=[O:17])[C:26]4=[O:40])[CH2:39][CH2:38]2)[CH2:50][CH2:49]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 44597070HCID 44597070, compound

Product 1

HCID 25127070HCID 25127070, compoundYield 22.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

According to the method of M. L. Gillaspy, B. A. Lefke, W. A. Hada, D. J. Hoover, Tetrahedron Letters 1995, 7399-7402, Cpd 30 (50 mg, 0.085 mmol), acetic acid (0.050 mL, 0.87 mmol), 3 Å molecular sieves (230 mg), [(1-ethoxycyclopropyl)oxy]trimethylsilane (0.102 mL, 0.51 mmol) were combined in methanol (4 mL) at rt. Sodium cyanoborohydride (24 mg, 0.38 mmol) was added and the reaction mixture was heated at reflux overnight, cooled to RT, filtered, and concentrated. The residue was dissolved in EtOAc (25 mL), washed with 2 N sodium hydroxide solution (2×10 mL) and brine (2×10 mL), dried (Na2SO4), concentrated, and purified by reversed phase HPLC [Phenomenex, Kromasil C18, 10μ, 110 Å, 250×50 mm, gradient elution with 20-90% acetonitrile (0.16% TFA) in water (0.2% TFA)] to yield Cpd 7 (12 mg, 19%) as a TFA salt. 1H NMR (300 MHz, CDCl3) δ 7.63 (d, J=7.4 Hz, 1H), 7.59 (d, J=4 Hz, 1H), 7.52 (d, J=4 Hz, 1H), 7.47 (t, J=7.8 Hz, 1H), 7.18 (d, J=7.8 Hz, 1H), 7.13 (t, J=4 Hz, 1H), 6.99 (br d, J=8.2 Hz, 1H), 6.92 (br s, 1H), 6.86 (d, J=8.2 Hz, 1H), 5.56 (br t, J=7.5 Hz, 1H), 4.34 (d, J=17 Hz, 1H), 3.93 (buried d, J=17 Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 3.7-2.9 (m, 11H), 2.66 (s, 3H), 2.5-2.0 (m, 6H), 1.7 (m, 2H); LC/MS (ES+) m/z 625.3 (M+1).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux overnight
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in EtOAc (25 mL)
  6. washwashed with 2 N sodium hydroxide solution (2×10 mL) and brine (2×10 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. custompurified by reversed phase HPLC [Phenomenex, Kromasil
  10. wash10μ, 110 Å, 250×50 mm, gradient elution with 20-90% acetonitrile (0.16% TFA) in water (0.2% TFA)]

Sources & evidence

ORD record
ord-05cbd04a9b31418494dfe19e5e33c5dc
Source dataset
uspto-grants-2013_05
Patent number
US08445514B2

Reaction notes

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