Methanol → HCID 45272335, compound

HRID 574313Notes

Reaction equation

HRID 574313 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([N:10]3[CH2:15][CH2:14][N:13]([CH2:16][C:17]([N:19]([CH:23]4[CH2:32][CH2:31][C:30]5[C:25](=[CH:26][C:27]([O:33]C)=[CH:28][CH:29]=5)[CH2:24]4)[CH2:20][CH2:21][CH3:22])=O)[CH2:12][CH2:11]3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.B.C1COCC1.CO>C1COCC1>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([N:10]3[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][N:19]([CH2:20][CH2:21][CH3:22])[CH:23]4[CH2:24][C:25]5[CH:26]=[C:27]([OH:33])[CH:28]=[CH:29][C:30]=5[CH2:31][CH2:32]4)[CH2:14][CH2:15]3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1

Participants

5

Reactant 3

HCID 887MethanolHCID 2723981Borane;tetrahydrofuranHCID 67504437HCID 67504437, compound

Product 1

HCID 45272335HCID 45272335, compoundYield 9.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring cold solution of compound 51 (220 mg, 0.492 mmol) in dry THF was added BH3.THF (211 mg, 2.46 mmol) and the reaction mixture was refluxed overnight. After cooling the reaction mixture to room temperature, 1 ml of methanol was added and the solvent was evaporated. The residue was dissolved in 15 ml of conc. HBr and refluxed for 1 h. The solvent was evaporated and the crude product was dissolved in dichloromethane (50 ml). The organic layer was washed with saturated NaHCO3 (30 ml) and dried over Na2SO4. The solvent was evaporated and the crude product was purified by flash column chromatography over silica gel using ethyl acetate/MeOH/Et3N (95:5:0.2) to afford 52 (20 mg). 1H NMR (400 MHz, CD3OD) δ 0.95 (t, 3H, J=7.6 Hz), 1.53-1.67 (m, 3H), 2.08 (d, 1H, J=9.6 Hz), 2.60-2.88 (m, 14H), 3.10-3.13 (m, 5H), 6.35 (d, 1H, J=2.8 Hz), 6.52-6.55 (m, 2H), 6.87 (d, 1H, J=8.8 Hz), 6.91-6.94 (dd, 1H, J=8.8 Hz and 2.4 Hz), 7.16-7.17 (m, 2H), 7.29 (d, 1H, J=8.8 Hz). Free base converted into oxalate salt, m.p. 179-183° C.

Workup

  1. temperaturethe reaction mixture was refluxed overnight
  2. customthe solvent was evaporated
  3. dissolutionThe residue was dissolved in 15 ml of conc. HBr
  4. temperaturerefluxed for 1 h
  5. customThe solvent was evaporated
  6. dissolutionthe crude product was dissolved in dichloromethane (50 ml)
  7. washThe organic layer was washed with saturated NaHCO3 (30 ml)
  8. dry with materialdried over Na2SO4
  9. customThe solvent was evaporated
  10. customthe crude product was purified by flash column chromatography over silica gel

Sources & evidence

ORD record
ord-16f1f7d406744293a1ea013dd3ed04b4
Source dataset
uspto-grants-2015_05
Patent number
US09034877B2

Reaction notes

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