Acetic Acid → tert-butyl 4-allyl-4-((1-tosyl-1H-indol-3-yl)methylamino)piperidine-1-carboxylate

HRID 41567

Reaction equation

HRID 41567 reaction equation
[S:1]([N:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]([CH:20]=O)=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[CH2:22]([C:25]1([NH2:38])[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)[CH:23]=[CH2:24].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH2:22]([C:25]1([NH:38][CH2:20][C:13]2[C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:11]([S:1]([C:4]3[CH:5]=[CH:6][C:7]([CH3:8])=[CH:9][CH:10]=3)(=[O:3])=[O:2])[CH:12]=2)[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)[CH:23]=[CH2:24]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 7358171-(4-Methylbenzene-1-sulfonyl)-1H-indole-3-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 67287394741687-08-1

Product 1

HCID 67252781tert-butyl 4-allyl-4-((1-tosyl-1H-indol-3-yl)methylamino)piperidine-1-carboxylateYield 60.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 1-tosyl-1H-indole-3-carbaldehyde [50562-79-3] (1.90 g, 6.35 mmol) in 1,2-dichloroethane (30 mL) were added tert-butyl 4-allyl-4-aminopiperidine-1-carboxylate [741687-08-1] (1.52 g, 6.35 mmol) and acetic acid (381 mg, 6.35 mmol). The resulting solution was heated at 60° C. for 3 h. Then NaBH(OAc)3 was added and the reaction mixture was heated at 60° C. for 38 h. The mixture was cooled to rt, saturated NaHCO3 solution (30 mL) was added and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water and brine, then dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude mixture was purified by flash-column chromatography over silicagel (eluent: 20% ethyl acetate/hexane) to yield the title compound (2.0 g, 60%). [LCMS RtE=0.34 min, [M+H]+=524.0]

Workup

  1. temperaturethe reaction mixture was heated at 60° C. for 38 h
  2. temperatureThe mixture was cooled to rt
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude mixture was purified by flash-column chromatography over silicagel (eluent: 20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f507aec85ad84e9ca7dc89d2e278bfa1
Source dataset
uspto-grants-2013_09
Patent number
US08530648B2

Linked notes

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