Sodium Sulfate → 1,1-Dimethylethyl 4-{[(5-chloro-6-methyl-3-pyridinyl)methyl]amino}-1-piperidinecarboxylate

HRID 420734Notes

Reaction equation

[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:23]=O)[CH:19]=[N:20][C:21]=1[CH3:22].[O-]S([O-])(=O)=O.[Na+].[Na+].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[Cl:15][C:16]1[CH:17]=[C:18]([CH2:23][NH:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)[CH:19]=[N:20][C:21]=1[CH3:22]

Participants

Conditions

Temperature: 90 °C

Procedure

A solution of 1,1-dimethylethyl 4-amino-1-piperidinecarboxylate (11.19 g, 55.9 mmol), 5-chloro-6-methyl-3-pyridinecarbaldehyde (for a synthesis see WO2006/137485 A1 Example 256) (7.82 g, 50.3 mmol) and Na2SO4 (8.73 g, 61.5 mmol) in DCE (200 ml) was stirred at 90° C. for 4.5 h and at room temperature overnight. NaBH(OAc)3 (35.5 g, 168 mmol) was added portionwise for 7 h until imine was not detected by LCMS analysis. 10% NaHCO3 was added and the organic phase was extracted twice with DCM, washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure to give 1,1-dimethylethyl 4-{[(5-chloro-6-methyl-3-pyridinyl)methyl]amino}-1-piperidinecarboxylate (18.7 g, 94%) as a yellow oil.

Workup

extractionthe organic phase was extracted twice with DCM
washwashed with brine
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-aba675aa3f3d4a04939c0bf9b5a4a113
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08097628B2

Reaction notes

Loading…