Acetic Acid → Tert-butyl 4-[(3-chlorophenyl)methyl]piperazine-1-carboxylate

HRID 1990909

Reaction equation

HRID 1990909 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=1)[CH:18]=O.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>ClC(Cl)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:18][C:17]2[CH:20]=[CH:21][CH:22]=[C:15]([Cl:14])[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 114773-ChlorobenzaldehydeHCID 14798Sodium HydroxideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 4316940Tert-butyl 4-[(3-chlorophenyl)methyl]piperazine-1-carboxylateYield 87.4%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of piperazine-1-carboxylic acid tert-butyl ester (4.00 g, 21.5 mmol) in dry dichloroethane (70 mL) are added 3-chlorobenzaldehyde (2.49 mL, 3.08 g, 21.9 mmol), HOAc (2.58 mL, 2.71 g, 45.1 mmol) and NaBH(OAc)3 (5.46 g, 25.8 mmol) at ambient temperature. After stirring at ambient temperature for 3d, 2N NaOH (40 mL) is added, the layers are separated, and the aqueous layer is extracted with CH2Cl2 (4×50 mL). The combined organic extracts are washed with water (3×50 mL) and brine (80 mL) and dried over MgSO4. The crude material is purified by chromatography on silica gel, eluting with hexane:EtOAc mixtures, yielding 5.83 g (18.8 mmol, 87%) of the title compound as yellow oil. MS (ES): m/z 311.0/313.0 (50/18) [MH+]. tR (method A)=5.0 min.

Workup

  1. additionis added
  2. customthe layers are separated
  3. extractionthe aqueous layer is extracted with CH2Cl2 (4×50 mL)
  4. washThe combined organic extracts are washed with water (3×50 mL) and brine (80 mL)
  5. dry with materialdried over MgSO4
  6. customThe crude material is purified by chromatography on silica gel
  7. washeluting with hexane

Sources & evidence

ORD record
ord-994156a864ae422b9ebe21fde113ac5d
Source dataset
uspto-grants-2010_01
Patent number
US07645754B2

Linked notes

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