Hydrochloric Acid → Tert-butyl 4-(2-chlorobenzylcarbamoyl)-4-(hydroxymethyl)piperidine-1-carboxylate

HRID 655948Notes

Reaction equation

HRID 655948 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][CH:26]=[CH:25][C:3]=1[CH2:4][NH:5][C:6]([C:8]1([C:21](OC)=[O:22])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1)=[O:7].[BH4-].[Li+].Cl>C1COCC1.CO>[Cl:1][C:2]1[CH:28]=[CH:27][CH:26]=[CH:25][C:3]=1[CH2:4][NH:5][C:6]([C:8]1([CH2:21][OH:22])[CH2:9][CH2:10][N:11]([C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])[CH2:12][CH2:13]1)=[O:7]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4148881Lithium borohydrideHCID 597785641-Tert-butyl 4-methyl 4-(2-chlorobenzylcarbamoyl)piperidine-1,4-dicarboxylate

Product 1

HCID 59778532Tert-butyl 4-(2-chlorobenzylcarbamoyl)-4-(hydroxymethyl)piperidine-1-carboxylateYield 84.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-tert-butyl 4-methyl 4-(2-chlorobenzylcarbamoyl)piperidine-1,4-dicarboxylate (2.8 g, 6.8 mmol) in THF (20 mL) and CH3OH (10 mL) was added lithium borohydride (1.4 g, 68 mmol, 10 equiv.). The reaction mixture was stirred for 3 h and neutralized with HCl (1N). The residue was partitioned between EtOAc and H2O. The organic layer was dried over Na2SO4 and concentrated to purify on RP-HPLC using a mixture of acetonitrile and H2O to give tert-butyl 4-(2-chlorobenzylcarbamoyl)-4-(hydroxymethyl)piperidine-1-carboxylate (2.2 g, 84%). LRMS (M-tBu+H+) m/z 327.0.

Workup

  1. customThe residue was partitioned between EtOAc and H2O
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customto purify on RP-HPLC
  5. additiona mixture of acetonitrile and H2O

Sources & evidence

ORD record
ord-4996b62d95e14ebf91bb99f293bf8cee
Source dataset
uspto-grants-2011_12
Patent number
US08071625B2

Reaction notes

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