Dimethylformamide → tert-Butyl indoline-1-carboxylate

HRID 857000Notes

Reaction equation

HRID 857000 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:6][CH2:5]2.CN(C=O)C.C([Li])(C)(C)C.CCCCC>C1COCC1.CCOC(C)=O.CC(O)=O>[C:14]([O:13][C:11]([N:7]1[C:8]2[C:4](=[CH:3][CH:2]=[CH:10][CH:9]=2)[CH2:5][CH2:6]1)=[O:12])([CH3:17])([CH3:15])[CH3:16]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 8003PentaneHCID 21865438tert-butyl 5-bromo-2,3-dihydro-1H-indole-1-carboxylateHCID 178418306HCID 178418306, compound

Product 1

HCID 3663954tert-Butyl indoline-1-carboxylateYield 18.4%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

5-Bromo-1-t-butyloxycarbonylindoline (2.0 g, 6.7 mmol) and DMF (0.53 mL, 6.7 mmol), were dissolved in THF (30 mL) and the resulting solution was cooled to −78° C. with stirring under a nitrogen atmosphere. A solution of t-butyllithium in pentane (1.7 M, 10.3 mL, 17.5 mmol) was added dropwise over 5 min. The reaction mixture was stirred for 2 h; then HOAc (3 mL) was added. The cloudy mixture was warmed to ambient temperature over 30 min and diluted with EtOAc (100 mL). Successive washings with a saturated Na2CO3 solution (2×10 mL) and then brine (10 mL) were performed. Drying over Na2SO4, filtration and removal of solvent in vacuo gave an oil. Column chromatography (EtOAc:hexane: 1:9, then 1:1) and removal of solvent in vacuo provided two products, both were white solids: (1) 1-t-butyloxycarbonylindoline (270 mg, 18% yield): 1H NMR (CDCl3, 300 MHz): 7.18–7.10 (m, 2H), 6.92 (t, 1H, J=7), 3.97 (t, 2H, J=7), 3.08 (t, 3H, J=7), 1.57 (s, 9H); MS (APCI+): 220 (C13H18NO2, M++H) and (2) the title product (650 mg, 39% yield): 1H NMR (CDCl3, 300 MHz): 9.86 (s, 1H), 7.9 (br s, 1H), 7.70–7.65 (m, 2H), 4.06 (t, 2H, J=7), 3.15 (t, 2H, J=7), 1.58 (s, 9H); MS (ES+): 248 (C14H18NO3, M++H).

Workup

  1. stirringThe reaction mixture was stirred for 2 h
  2. temperatureThe cloudy mixture was warmed to ambient temperature over 30 min
  3. washSuccessive washings with a saturated Na2CO3 solution (2×10 mL)
  4. dry with materialDrying over Na2SO4, filtration and removal of solvent in vacuo
  5. customgave an oil
  6. customColumn chromatography (EtOAc:hexane: 1:9, then 1:1) and removal of solvent in vacuo
  7. customprovided two products

Sources & evidence

ORD record
ord-81b81013338d4f1d9cde37cdc5eee821
Source dataset
uspto-grants-2006_12
Patent number
US07144894B2

Reaction notes

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