Tetrahydrofuran → Tert-butyl 5-(2-oxo-1-piperidinyl)-1-indolinecarboxylate

HRID 890518Notes

Reaction equation

HRID 890518 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([NH2:17])=[CH:14][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:19][CH2:20][CH2:21][CH2:22][C:23](Cl)=[O:24].C1COCC1.CC(C)([O-])C.[K+]>O>[O:24]=[C:23]1[CH2:22][CH2:21][CH2:20][CH2:19][N:17]1[C:13]1[CH:12]=[C:11]2[C:16](=[CH:15][CH:14]=1)[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH2:10]2

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 5211735-Bromovaleryl chloride2×HCID 22240520tert-Butyl 5-amino-2,3-dihydro-1H-indole-1-carboxylateHCID 23665647Potassium tert-butoxide3×

Product 1

HCID 22240498Tert-butyl 5-(2-oxo-1-piperidinyl)-1-indolinecarboxylateYield 50.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Part H. To tert-butyl-5-amino-1-indolinecarboxylate (1.90 g, 8.2 mmol) was added 5-bromovaleryl chloride (1.4 mL, 9.0 mmol) and 18 mL of THF. After stirring for 5 min at rt under N2, potassium tert-butoxide (9 mL, 9 mmol; 1.0 M in THF) was added in one portion, and the resulting brown solution was stirred under N2 for 30 min. A second portion of potassium tert-butoxide (9 mL) was added, and the resulting brown suspension was stirred for 15 min. An additional 0.10 mL-portion of 5-bromovaleryl chloride and a 4.5 mL-portion of potassium tert-butoxide were added, and the mixture was stirred for 30 min. The reaction was then poured into H2O (80 mL). The aqueous layer was washed with EtOAc (3×50 mL), and the combined organic layers were washed with brine, dried over Na2SO4, and filtered. The filtrate was concentrated and the resulting residue was purified by radial chromatography (50% EtOAc in hexanes) to afford tert-butyl 5-(2-oxo-1-piperidinyl)-1-indolinecarboxylate as a pink solid (1.30 g, 50%). LRMS (AP+): 317.2 (M+H)+. 1H NMR (CDCl3) δ 7.40–7.80 (br m, 1H), 7.01 (s, 1H), 6.97 (d, 1H), 3.94 (t, 2H), 3.55 (br m, 2H), 3.09 (t, 2H), 2.49 (br m, 2H), 1.91 (br m, 4 H), 1.52 (s, 9H).

Workup

  1. stirringthe resulting brown solution was stirred under N2 for 30 min
  2. stirringthe resulting brown suspension was stirred for 15 min
  3. stirringthe mixture was stirred for 30 min
  4. washThe aqueous layer was washed with EtOAc (3×50 mL)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated
  9. customthe resulting residue was purified by radial chromatography (50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5602022a24eb4ca7a9d2c45e4ec3818f
Source dataset
uspto-grants-2006_02
Patent number
US06995172B2

Reaction notes

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