Triphenylphosphine → methyl 1-[1-(tert-butoxycarbonyl)piperidin-4-yl]-7-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylate

HRID 626871Notes

Reaction equation

HRID 626871 reaction equation
[O:1]=[C:2]1[C:10]2[NH:9][CH:8]=[C:7]([C:11]([O:13][CH3:14])=[O:12])[C:6]=2[CH2:5][CH2:4][CH2:3]1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25](O)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([N:9]2[C:10]3[C:2](=[O:1])[CH2:3][CH2:4][CH2:5][C:6]=3[C:7]([C:11]([O:13][CH3:14])=[O:12])=[CH:8]2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 11776Triphenylphosphine2×HCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 68276513Methyl 7-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylate

Product 1

HCID 68276515methyl 1-[1-(tert-butoxycarbonyl)piperidin-4-yl]-7-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylateYield 71.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of methyl 7-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylate (100 mg 0.52 mmol), tert-butyl-4-hydroxypiperidine-1-carboxylate (105 mg, 0.52 mmol), and triphenylphosphine (136 mg, 0.52 mmol), in anhydrous THF (5 mL) at room temperature, was added di tert-butyl-diazadicarboxylate (DTAD) (120 mg, 0.52 mmol). The mixture was stirred at room temperature for 8 h. HPLC/MS suggested 40% conversion and 60% SM remained. Reagents were added, triphenylphosphine (136 mg, 0.52 mmol) and DTAD (120 mg, 0.52 mmol), the mixture was stirred for 4 hours. HPLC/MS showed 80% conversion and 20% SM remained. Reagents were re-added TPP (136 mg, 0.52 mmol) and DTAD (120 mg, 0.526 mmol) and the solution was stirred for additional 4 hours. The volatiles were removed in vacuo, the crude solid was purified by flash chromatography on silica gel (hexane/EtOAc 7/3) to afford 140 mg (70% yield) of the title compound as a white solid.

Workup

  1. additionReagents were added
  2. additionReagents were re-added TPP (136 mg, 0.52 mmol) and DTAD (120 mg, 0.526 mmol)
  3. stirringthe solution was stirred for additional 4 hours
  4. customThe volatiles were removed in vacuo
  5. customthe crude solid was purified by flash chromatography on silica gel (hexane/EtOAc 7/3)

Sources & evidence

ORD record
ord-dd3a971292a741acae817aa7698e3877
Source dataset
uspto-grants-2016_04
Patent number
US09309253B2

Reaction notes

Loading…