Acetic Acid → 1,1-Dimethylethyl 4-cyano[1,4′-bipiperidine]-1′-carboxylate

HRID 599726Notes

Reaction equation

HRID 599726 reaction equation
[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].O=[C:16]1[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1.[C:29]([CH:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1)#[N:30].CC(O)=O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl.O>[C:29]([CH:31]1[CH2:36][CH2:35][N:34]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH2:33][CH2:32]1)#[N:30]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 311Citric AcidHCID 1382234-CyanopiperidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 672736071,1-Dimethylethyl 4-cyano[1,4′-bipiperidine]-1′-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

6.09 g (27.3 mmol) of NaBH(OAc)3 were added batchwise to a suspension, cooled to 0° C., of 5.44 g (27.3 mmol) tert.butyl 4-oxo-piperidin-1-carboxylate, 3.00 g (27.2 mmol) 4-cyanopiperidine and 1.6 mL (28.0 mmol) AcOH in 400 mL DCM and the reaction mixture was stirred overnight, while warming up to RT. 400 mL water were added and the mixture was acidified with citric acid. The organic phase was separated off, the aqueous phase was made alkaline with saturated NaHCO3 solution and extracted exhaustively with DCM. The combined organic phases were concentrated by evaporation i. vac. and the residue was crystallised with a little DIPE.

Workup

  1. customThe organic phase was separated off
  2. extractionextracted exhaustively with DCM
  3. concentrationThe combined organic phases were concentrated by evaporation i
  4. customand the residue was crystallised with a little DIPE

Sources & evidence

ORD record
ord-84f7c43108e947898e53d3f69177bf27
Source dataset
uspto-grants-2011_03
Patent number
US07897603B2

Reaction notes

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