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

HRID 2174121Notes

Reaction equation

HRID 2174121 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH2:11][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]4[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[N:8][C:7]=2[CH:31]=1)#[N:2].CC(C)([O-])C.[K+].C1OCCOCCOCCOCCOCCOC1.[C:56]([O:60][CH2:61][CH3:62])(=[O:59])[CH:57]=[CH2:58].[Cl-].[NH4+]>C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([CH:11]([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]4[C:24]([O:26][C:27]([CH3:28])([CH3:30])[CH3:29])=[O:25])[CH2:58][CH2:57][C:56]([O:60][CH2:61][CH3:62])=[O:59])=[N:8][C:7]=2[CH:31]=1)#[N:2]

Participants

7

Reactant 5

HCID 8821Ethyl AcrylateHCID 25517Ammonium ChlorideHCID 2855718-Crown-6HCID 23665647Potassium tert-butoxideHCID 86701743tert-Butyl 4-((5-cyanobenzo[d]oxazol-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701763(+/-)-tert-Butyl 4-(1-(5-cyanobenzo[d]oxazol-2-yl)-4-ethoxy-4-oxobutyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Procedure

A solution of tert-butyl 4-((5-cyanobenzo[d]oxazol-2-yl)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 144-A) (189 mg, 0.453 mmol) in THF (1.7 mL) was added to a solution of potassium tert-butoxide (50.8 mg, 0.453 mmol) in THF (1.7 mL) under nitrogen at −78° C. After stirring for 15 min a solution 18-crown-6 (11.97 mg, 0.045 mmol) in THF (566 μl) was added to the mixture at the same temperature and the reaction was then stirred for another 15 min. At this point ethyl acrylate (61.5 μl, 0.679 mmol) in THF (566 μl) was added dropwise. After 25 minutes, the reaction mixture was poured into a solution of saturated ammonium chloride, extracted with EtOAc (2×), passed through a phase separator and concentrated and purified via FCC with Heptane/AcOEt (100/0 to 70/30) to afford the title compound. MS (ESI+) m/z 418.4 (M+H-Boc).

Workup

  1. additionwas added to the mixture at the same temperature
  2. waitAfter 25 minutes
  3. extractionextracted with EtOAc (2×)
  4. concentrationconcentrated
  5. custompurified via FCC with Heptane/AcOEt (100/0 to 70/30)

Sources & evidence

ORD record
ord-2c43ad3a6a524bbda389970b50a67363
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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