tert-Butyl 4-oxopiperidine-1-carboxylate → HCID 69156905, compound

HRID 967401Notes

Reaction equation

HRID 967401 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:9][CH:10]([O:13][CH3:14])[O:11][CH3:12])=[C:6]([NH2:8])[CH:7]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][C:25](=O)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([NH:8][C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[CH2:9][CH:10]([O:13][CH3:14])[O:11][CH3:12])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 22293846HCID 22293846, compound

Product 1

HCID 69156905HCID 69156905, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred solution of 2 g of 5-chloro-2-(2,2-dimethoxy-ethyl)-phenylamine, (9.27 mmol) in 50 mL of acetic acid was added 3.7 g of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (18.5 mmol). The reaction mixture was allowed to stir for 1 h at room temperature before the portion wise addition of 5.9 g of sodium triacetoxyborohydride (27.9 mmol). The reaction mixture was allowed to stir an additional 5 h before removing the solvent under reduced pressure. The crude product was partitioned between CH2Cl2 (250 mL) and water. The aqueous layer was further extracted with CH2Cl2 (2×75 mL). The combined organic layers were then washed with 1 N NaOH (2×50 mL), brine, dried over Na2SO4, and concentrated. Purification by chromatography (silica, 10-25% EtOAc/hexanes) afforded 1.5 g (71%) of desired product. TLC (silica, 35% EtOAc/hexanes): Rf=0.49. MS (electrospray): exact mass calculated for C20H31ClN2O4, 398.20. m/z found, 399.2 [M+H]+. 1H NMR (CDCl3, 400 MHz): 6.94 (d, J=7.83 Hz, 1H), 6.61 (dd, J=7.83, 2.02 Hz, 1H), 6.57 (d, J=2.02 Hz, 1H), 4.87 (br s, 1H), 4.40 (t, J=5.31 Hz, 1H), 3.97 (br m, 2H), 3.36 (s, 6H), 3.02 (m, 2H), 2.78 (d, J=5.05 Hz, 2H), 2.00 (m, 2H), 1.47 (s, 9H), 1.37 (m, 2H).

Workup

  1. custombefore removing the solvent under reduced pressure
  2. customThe crude product was partitioned between CH2Cl2 (250 mL) and water
  3. extractionThe aqueous layer was further extracted with CH2Cl2 (2×75 mL)
  4. washThe combined organic layers were then washed with 1 N NaOH (2×50 mL), brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by chromatography (silica, 10-25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-681ceb0d636742a4a9df4759a159c531
Source dataset
uspto-grants-2005_10
Patent number
US06953793B2

Reaction notes

Loading…