Methyl iodide → (+/-)-tert-Butyl 4-(2-(5-cyanobenzo[d]oxazol-2-yl)-1-ethoxy-1-oxopropan-2-yl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

HRID 2174106Notes

Reaction equation

HRID 2174106 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH:11]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][N:21]4[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:8][C:7]=2[CH:36]=1)#[N:2].[CH3:37]I.[H-].[Na+]>CN(C=O)C>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([C:17]3[C:25]([O:26][CH3:27])=[CH:24][C:23]([CH3:28])=[C:22]4[C:18]=3[CH:19]=[CH:20][N:21]4[C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])([CH3:37])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:8][C:7]=2[CH:36]=1)#[N:2]

Participants

5

Reactant 3

HCID 6328Methyl iodide2×HCID 24758Sodium hydrideHCID 86701744(+/-)-tert-Butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)-2-ethoxy-2-oxoethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701745(+/-)-tert-Butyl 4-(2-(5-cyanobenzo[d]oxazol-2-yl)-1-ethoxy-1-oxopropan-2-yl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (±)-tert-butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)-2-ethoxy-2-oxoethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 144-B) (139.5 mg, 0.285 mmol) in DMF (2.850 mL) were added successively MeI (0.080 mL, 1.282 mmol) and NaH (34.2 mg, 0.855 mmol) at 0° C. After stirring for 2.5 hrs at this temperature another additional aliquot of MeI (0.045 mL, 0.57 mmol) were added to the mixture. The mixture was allowed to stir at room temperature overnight. The reaction mixture was quenched with a saturated aq. solution of ammonium chloride at 0° C. and the layers were separated. The aqueous layer was extracted with AcOEt and the combined organic layers were concentrated to give crude product that was purified via FCC: Heptane/AcOEt:100/0 to 50/50 to obtain the title compound. MS (ESI+) m/z 504.38 (M+H).

Workup

  1. additionwere added to the mixture
  2. customThe reaction mixture was quenched with a saturated aq. solution of ammonium chloride at 0° C.
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with AcOEt
  5. concentrationthe combined organic layers were concentrated
  6. customto give crude product that
  7. customwas purified via FCC

Sources & evidence

ORD record
ord-6393a603d68b4314a9ef66358574a0a6
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

Loading…