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

HRID 2174123Notes

Reaction equation

HRID 2174123 reaction equation
CC(C)([O-])C.[K+].[C:7]([C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([CH:17]([C:19]3[C:27]([O:28][CH3:29])=[CH:26][C:25]([CH3:30])=[C:24]4[C:20]=3[CH:21]=[CH:22][N:23]4[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH3:18])=[N:14][C:13]=2[CH:38]=1)#[N:8].C1OCCOCCOCCOCCOCCOC1.[C:57]([O:61][CH3:62])(=[O:60])[CH:58]=[CH2:59]>C1COCC1>[C:7]([C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([C:17]([C:19]3[C:27]([O:28][CH3:29])=[CH:26][C:25]([CH3:30])=[C:24]4[C:20]=3[CH:21]=[CH:22][N:23]4[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])([CH2:59][CH2:58][C:57]([O:61][CH3:62])=[O:60])[CH3:18])=[N:14][C:13]=2[CH:38]=1)#[N:8]

Participants

6

Reactant 4

HCID 7294Methyl AcrylateHCID 2855718-Crown-6HCID 23665647Potassium tert-butoxideHCID 86701764(+/-)-tert-Butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701765(+/-)-tert-Butyl 4-(2-(5-cyanobenzo[d]oxazol-2-yl)-5-methoxy-5-oxopentan-2-yl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

To a mixture of potassium tert-butoxide (15.60 mg, 0.139 mmol) in THF (329 μl) at −78° C. under nitrogen was added (±)-tert-butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)ethyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 150-A) (50 mg, 0.116 mmol) in THF (659 μL). After stirring for 5 min a solution of 18-crown-6 (3.06 mg, 0.012 mmol) in THF (412 μl) that was degassed and placed under nitrogen was added to the mixture at the same temperature and stirred for another 5 min. Then a solution of methyl acrylate (210 μl, 2.318 mmol) in THF (329 μl) was degassed and added dropwise and stirred at the same temp for 30 min. The reaction mixture was allowed to reach rt over 1 hr and then was stirred at rt for 30 hrs. The reaction mixture was quenched with a saturated solution of ammonium chloride, diluted with DCM and water, passed through a phase separator and concentrated to give the title compound that was taken to the next step without further purification. MS (ESI+) m/z 518.5 (M+H).

Workup

  1. customwas degassed
  2. additionwas added to the mixture at the same temperature
  3. additionadded dropwise
  4. stirringstirred at the same temp for 30 min
  5. waitto reach rt over 1 hr
  6. stirringwas stirred at rt for 30 hrs
  7. customThe reaction mixture was quenched with a saturated solution of ammonium chloride
  8. additiondiluted with DCM and water
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-15900b1441c34a8f84bb54b86f353a0d
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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