18-Crown-6 → (+/-)-tert-Butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)-3-methoxy-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

HRID 2174117Notes

Reaction equation

HRID 2174117 reaction equation
CC(C)([O-])C.[K+].[C:7]([C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([CH2:17][C:18]3[C:26]([O:27][CH3:28])=[CH:25][C:24]([CH3:29])=[C:23]4[C:19]=3[CH:20]=[CH:21][N:22]4[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[N:14][C:13]=2[CH:37]=1)#[N:8].C1OCCOCCOCCOCCOCCOC1.Br[CH2:57][C:58]([O:60][CH3:61])=[O:59]>C1COCC1>[C:7]([C:9]1[CH:10]=[CH:11][C:12]2[O:16][C:15]([CH:17]([C:18]3[C:26]([O:27][CH3:28])=[CH:25][C:24]([CH3:29])=[C:23]4[C:19]=3[CH:20]=[CH:21][N:22]4[C:30]([O:32][C:33]([CH3:34])([CH3:36])[CH3:35])=[O:31])[CH2:57][C:58]([O:60][CH3:61])=[O:59])=[N:14][C:13]=2[CH:37]=1)#[N:8]

Participants

6

Reactant 4

HCID 2855718-Crown-6HCID 60984Methyl bromoacetateHCID 23665647Potassium tert-butoxideHCID 86701743tert-Butyl 4-((5-cyanobenzo[d]oxazol-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701760(+/-)-tert-Butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)-3-methoxy-3-oxopropyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

To a mixture of potassium tert-butoxide (108 mg, 0.958 mmol) in THF (0.715 mL) at −78° C. under nitrogen was added tert-butyl 4-((5-cyanobenzo[d]oxazol-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 144-A) (200 mg, 0.479 mmol) in THF (4.3 mL) under nitrogen. After stirring for 15 min a solution of 18-crown-6 (12.66 mg, 0.048 mmol) in THF (1.430 mL) was added to the mixture at the same temperature and stirred for another 15 min. Then a solution of methyl bromoacetate (0.618 mL, 6.71 mmol) in THF (0.715 mL) was degassed and added dropwise and stirred at the same temp for 10 min. The reaction mixture was quenched with a saturated solution of ammonium chloride, extracted with EtOAc (2×), passed through a phase separator and concentrated to give the title compound. MS (ESI+) m/z 490.32 (M+H).

Workup

  1. additionwas added to the mixture at the same temperature
  2. additionadded dropwise
  3. stirringstirred at the same temp for 10 min
  4. customThe reaction mixture was quenched with a saturated solution of ammonium chloride
  5. extractionextracted with EtOAc (2×)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-19d17045b65f4b0f9efc60df25395c25
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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