Methanol → HCID 67248100, compound

HRID 1896115Notes

Reaction equation

HRID 1896115 reaction equation
[Cl:1][C:2]1[C:3]([Cl:25])=[CH:4][C:5]2[N:11]3[CH2:12][CH2:13][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:15][CH:10]3[CH2:9][C:8](=O)[NH:7][C:6]=2[CH:24]=1.B.CO>O1CCCC1>[Cl:1][C:2]1[C:3]([Cl:25])=[CH:4][C:5]2[N:11]3[CH2:12][CH2:13][N:14]([C:16]([O:18][C:19]([CH3:20])([CH3:21])[CH3:22])=[O:17])[CH2:15][CH:10]3[CH2:9][CH2:8][NH:7][C:6]=2[CH:24]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 6331BoraneHCID 67247361HCID 67247361, compound

Product 1

HCID 67248100HCID 67248100, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of Example 15B (168 mg, 0.435 mmol) in tetrahydrofuran (1.5 mL) was added borane in tetrahydrofuran (1.74 mL, 1 M solution). The resulting mixture was heated to 80° C. overnight. Methanol was then added, and the mixture was heated at 80° C. for 1 hour to destroy excess borane. The reaction was then cooled to room temperature and 1 M HCl was added. The mixture was allowed to stir for another 30 minutes. Aqueous sodium bicarbonate was slowly added to the mixture until the solution was basic (pH=8). Ethyl acetate was then added, and the water layer was separated and washed two times with additional ethyl acetate. The organic layers thus obtained were combined and concentrated. The crude material was purified by silica gel chromatography eluting with a gradient of 0% to 30% ethyl acetate in hexane to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 6.88 (s, 1 H), 6.70 (s, 1 H), 5.75 (d, J=5.55 Hz, 1 H), 3.61-3.79 (m, 1 H), 3.36-3.58 (m, 2 H), 2.95-3.23 (m, 5 H), 2.82-2.94 (m, 1 H), 1.80-1.97 (m, 1 H), 1.56-1.74 (m, 1 H), 1.41 (s, 9 H); MS (DCI+) m/z 372.2 (M+H)+.

Workup

  1. temperaturethe mixture was heated at 80° C. for 1 hour
  2. customto destroy excess borane
  3. temperatureThe reaction was then cooled to room temperature
  4. addition1 M HCl was added
  5. additionAqueous sodium bicarbonate was slowly added to the mixture until the solution
  6. additionEthyl acetate was then added
  7. customthe water layer was separated
  8. washwashed two times with additional ethyl acetate
  9. customThe organic layers thus obtained
  10. concentrationconcentrated
  11. customThe crude material was purified by silica gel chromatography
  12. washeluting with a gradient of 0% to 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-827cf2f9770b44c2b4a714e8d5813dd8
Source dataset
uspto-grants-2013_08
Patent number
US08518933B2

Reaction notes

Loading…