Cesium carbonate → (+/-)-Ethyl 2-(5-cyanobenzo[d]oxazol-2-yl)-2-(5-methoxy-7-methyl-1H-indol-4-yl)propanoate

HRID 2174107Notes

Reaction equation

HRID 2174107 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([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]4C(OC(C)(C)C)=O)([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:8][C:7]=2[CH:37]=1)#[N:2].C(=O)([O-])[O-].[Cs+].[Cs+]>CCO>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([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][NH:22]4)([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[N:8][C:7]=2[CH:37]=1)#[N:2]

Participants

4

Reactant 2

HCID 10796Cesium carbonateHCID 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

Product 1

HCID 86701746(+/-)-Ethyl 2-(5-cyanobenzo[d]oxazol-2-yl)-2-(5-methoxy-7-methyl-1H-indol-4-yl)propanoate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (±)-tert-butyl 4-(2-(5-cyanobenzo[d]oxazol-2-yl)-1-ethoxy-1-oxopropan-2-yl)-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 144-C) (44 mg, 0.087 mmol) in EtOH (874 μL), was added cesium carbonate (142 mg, 0.437 mmol). The reaction mixture was heated up to 60° C. and stirred for 2 hrs. The reaction mixture was quenched with a saturated solution of sodium bicarbonate at 0° C. The layers were separated and the aqueous layer was extracted with EtOAc (2×). The combined organic layers were dried over magnesium sulfate and concentrated to give crude product that was purified via FCC (4 g column): Heptane/AcOEt: 100/0 to 50/50 to obtain the title compound. 1H NMR (600 MHz, DMSO-d6) δ ppm 11.05 (br. s., 1H) 8.36-8.60 (m, 1H) 7.72-8.02 (m, 2H) 7.13 (t, J=2.93 Hz, 1H) 6.81 (s, 1H) 5.12 (dd, J=3.21, 1.83 Hz, 1H) 4.02-4.28 (m, 2H) 3.62 (s, 3H) 2.43-2.48 (m, 3H) 2.03 (s, 3H) 1.08 (t, J=7.11 Hz, 3H). HRMS calcd. for C23H21N3O4 (M+H)+ 404.1610. found 404.1619.

Workup

  1. customThe reaction mixture was quenched with a saturated solution of sodium bicarbonate at 0° C
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc (2×)
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. concentrationconcentrated
  6. customto give crude product that
  7. customwas purified via FCC (4 g column)

Sources & evidence

ORD record
ord-c16c6eace92f4c4eaeee19abd03db80c
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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