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

HRID 2174079Notes

Reaction equation

HRID 2174079 reaction equation
C(OC([N:8]1[C:16]2[C:11](=[C:12]([C:20]([C:23]3[O:24][C:25]4[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][C:26]=4[N:27]=3)([OH:22])[CH3:21])[C:13]([O:18][CH3:19])=[CH:14][C:15]=2[CH3:17])[CH:10]=[CH:9]1)=O)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+]>CO>[OH:22][C:20]([C:23]1[O:24][C:25]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[CH:28][C:26]=2[N:27]=1)([C:12]1[C:13]([O:18][CH3:19])=[CH:14][C:15]([CH3:17])=[C:16]2[C:11]=1[CH:10]=[CH:9][NH:8]2)[CH3:21]

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 86701712tert-butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)-1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701713(-)-2-(1-hydroxy-1-(5-methoxy-7-methyl-1H-indol-4-yl)ethyl)benzo[d]oxazole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of (±)-tert-butyl-4-(1-(5-cyanobenzo[d]oxazol-2-yl)-1-hydroxyethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (6.5 mg, 0.019 mmol) and Cs2CO3 (146 mg, 0.447 mmol) in MeOH (0.5 mL) was heated at 60° C. and stirred for 30 min. The reaction mixture was cooled to rt, quenched with a saturated aq. solution of ammonium chloride, diluted with AcOEt and water. The layers were separated and the aq. layer was extracted with AcOEt. The combined organic layers were dried over MgSO4, filtered and evaporated to dryness. The resulting residue was purified by flash chromatography (0-50% EtOAc:heptanes) to give the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.88 (br. s., 1H) 8.36 (dd, J=1.39, 0.76 Hz, 1H) 7.65-8.00 (m, 2H) 7.28 (t, J=2.84 Hz, 1H) 6.95 (dd, J=3.03, 2.02 Hz, 1H) 6.62 (s, 1H) 6.31 (s, 1H) 3.19 (s, 3H) 2.44 (d, J=0.51 Hz, 3H) 1.95-2.02 (m, 3H). MS (ESI+) m/z 348.1 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. customquenched with a saturated aq. solution of ammonium chloride
  3. additiondiluted with AcOEt and water
  4. customThe layers were separated
  5. extractionthe aq. layer was extracted with AcOEt
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customThe resulting residue was purified by flash chromatography (0-50% EtOAc:heptanes)

Sources & evidence

ORD record
ord-43f7eda0b18745dbb490a7a9d8337d93
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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