Cesium carbonate → (+/-)-2-(hydroxy(5-methoxy-7-methyl-1H-indol-4-yl)methyl)benzo[d]oxazole-5-carbonitrile

HRID 2174076Notes

Reaction equation

HRID 2174076 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH:11]([OH:31])[C:12]3[C:20]([O:21][CH3:22])=[CH:19][C:18]([CH3:23])=[C:17]4[C:13]=3[CH:14]=[CH:15][N:16]4C(OC(C)(C)C)=O)=[N:8][C:7]=2[CH:32]=1)#[N:2].C([O-])([O-])=O.[Cs+].[Cs+]>CO.CCOC(C)=O>[OH:31][CH:11]([C:12]1[C:20]([O:21][CH3:22])=[CH:19][C:18]([CH3:23])=[C:17]2[C:13]=1[CH:14]=[CH:15][NH:16]2)[C:9]1[O:10][C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:32][C:7]=2[N:8]=1

Participants

5

Reactant 2

HCID 10796Cesium carbonateHCID 86701709tert-Butyl-4-((5-cyanobenzo[d]oxazol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701710(+/-)-2-(hydroxy(5-methoxy-7-methyl-1H-indol-4-yl)methyl)benzo[d]oxazole-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of tert-butyl 4-((5-cyanobenzo[d]oxazol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (1.10 g, 2.54 mmol) and Cs2CO3 (1.65 g, 5.08 mmol) in MeOH (25 mL) was allowed to stir at 60° C. for 4 h. The reaction mixture was cooled to rt and diluted with EtOAc (50 mL). The mixture was concentrated to half of the initial volume. The mixture was then diluted with brine and 1M aq. NaHSO4. The organic layer was separated. The aqueous layer was extracted with EtOAc. The combined organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel (heptane/EtOAc=100:0 to 30:70) to give the title compound. 1H NMR (400 MHz, CD3OD) δ ppm 8.08 (t, J=1.07 Hz, 1H), 7.68 (s, 2H), 7.17 (d, J=3.15 Hz, 1H), 6.77 (s, 1H), 6.69 (s, 1H), 6.53 (d, J=3.15 Hz, 1H), 3.81 (s, 3H), 2.50 (s, 3H). HRMS calcd. for C19H15N3O3 (M+H)+ 334.1192. found 334.1191.

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. concentrationThe mixture was concentrated to half of the initial volume
  3. additionThe mixture was then diluted with brine and 1M aq. NaHSO4
  4. customThe organic layer was separated
  5. extractionThe aqueous layer was extracted with EtOAc
  6. washThe combined organic phase was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash column chromatography on silica gel (heptane/EtOAc=100:0 to 30:70)

Sources & evidence

ORD record
ord-d875dae8dbc3470aacdce21ed5b6064f
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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