4-(N-Boc-amino)piperidine → HCID 68778000, compound

HRID 2191097Notes

Reaction equation

HRID 2191097 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]2[CH:18]=[C:17]([C:19]3[C:23]4[CH2:24][C:25]([CH3:30])([CH3:29])[CH2:26][C:27](=[O:28])[C:22]=4[S:21][C:20]=3[N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:16]=[CH:15][N:14]=2)[CH:8]=1)(=O)=O.C(OC([NH:46][CH:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1)=O)(C)(C)C.CC(C)([O-])C.[K+]>O1CCOCC1.CC(O)=O.CC(P(C(C)(C)C)C1C(C2[C-]=CC=CC=2)=CC=CC=1)(C)C.[Pd]>[NH2:46][CH:47]1[CH2:52][CH2:51][N:50]([C:7]2[CH:8]=[C:9]([C:13]3[CH:18]=[C:17]([C:19]4[C:23]5[CH2:24][C:25]([CH3:30])([CH3:29])[CH2:26][C:27](=[O:28])[C:22]=5[S:21][C:20]=4[N:31]4[CH2:32][CH2:33][O:34][CH2:35][CH2:36]4)[CH:16]=[CH:15][N:14]=3)[CH:10]=[CH:11][CH:12]=2)[CH2:49][CH2:48]1

Participants

6

Reactant 3

HCID 7238334-(N-Boc-amino)piperidineHCID 23665647Potassium tert-butoxideHCID 87571193HCID 87571193, compound

Product 1

HCID 68778000HCID 68778000, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 119822622-(2'-Di-tert-butylphosphine)biphenylpalladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of Example 360 (150 mg, 0.27 mmol), 4-(tert-butoxycarbonylamino)-piperidine (105 mg, 0.52 mmol), potassium tert-butoxide (45 mg, 0.37 mmol) and acetato(2′-di-tert-butylphosphino-1,1′-biphenyl-2-yl)palladium(II) (20 mg, 0.043 mmol) in 1,4-dioxane (6.0 mL) was heated in a sealed tube at 100° C., under microwave irradiation, for 30 minutes. The solvent was removed in vacuo and the residue was purified by column chromatography (SiO2, 0-100% EtOAc/heptane). A sample of the obtained solid (43 mg) was taken up in DCM (8.0 mL), treated with trifluoroacetic acid (2.0 mL) and stirred at room temperature for 4 h. The reaction mixture was partitioned between DCM (20 mL) and saturated aqueous sodium hydrogencarbonate solution (20 mL). The organic phase was dried (magnesium sulfate), the solvent was removed in vacuo and the residue was purified by column chromatography (0-20% MeOH/DCM, 1% NH4OH) to give the title compound (23 mg, 33%) as a clear glass. δH (CD3OD) 8.68 (1H, d, J 5.1 Hz), 7.91 (1H, s), 7.64-7.59 (1H, m), 7.46-7.33 (3H, m), 7.15-7.06 (1H, m), 3.87-3.77 (2H, m), 3.72-3.64 (4H, m), 3.10-3.00 (4H, m), 2.92-2.75 (3H, m), 2.63 (2H, s), 2.46 (2H, s), 2.01-1.90 (2H, m), 1.63-1.47 (2H, m), 1.04 (6H, s). LCMS (ES+) 517.3 (M+H)+.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was purified by column chromatography (SiO2, 0-100% EtOAc/heptane)
  3. additiontreated with trifluoroacetic acid (2.0 mL)
  4. customThe reaction mixture was partitioned between DCM (20 mL) and saturated aqueous sodium hydrogencarbonate solution (20 mL)
  5. dry with materialThe organic phase was dried (magnesium sulfate)
  6. customthe solvent was removed in vacuo
  7. customthe residue was purified by column chromatography (0-20% MeOH/DCM, 1% NH4OH)

Sources & evidence

ORD record
ord-8695b40eaa82419b8c705b6ce4d6d5fc
Source dataset
uspto-grants-2012_12
Patent number
US08324204B2

Reaction notes

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