Diisopropylamine → HCID 66742460, compound

HRID 2194158Notes

Reaction equation

HRID 2194158 reaction equation
C(NC(C)C)(C)C.[CH2:8]([O:10][C:11]([CH:13]1[CH2:18][CH2:17][N:16]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:15][CH2:14]1)=[O:12])[CH3:9].Br[CH2:27][CH2:28][O:29][CH3:30]>C1COCC1.CCCCCC.C(OCC)(=O)C>[CH2:8]([O:10][C:11]([C:13]1([CH2:27][CH2:28][O:29][CH3:30])[CH2:14][CH2:15][N:16]([CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:17][CH2:18]1)=[O:12])[CH3:9]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 809722-Bromoethyl methyl etherHCID 90423Ethyl 1-benzylpiperidine-4-carboxylate

Product 1

HCID 66742460HCID 66742460, compoundYield 85.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-5 °C

Procedure

To a solution of diisopropylamine (5.68 ml, 0.040 mol) in 100 ml THF at −78° C. was added nBuli (1.6M solution in hexane, 25.9 ml, 0.041 mol) drop-wise. The reaction mixture was warmed to −5° C. and stirring was continued for 30 mins. A solution of 1-benzylpiperidine-4-carboxylic acid ethyl ester (5.00 g, 0.020 mol) in THF (20 ml) was added drop wise and stirring was continued for a further 3 hr followed by the addition of a solution of 1-bromo-2-methoxy-ethane (3.82 g, 0.040 mol) in THF (20 ml) at −5° C. The reaction mixture was then allowed to warm to room temperature and stirring was continued overnight. The reaction mixture was quenched with water and concentrated in vacuo to give a brown residue which was diluted with ethyl acetate and extracted 1N HCl. The aqueous layers were then combined, made basic (with 1N NaOH) and extracted with ethyl acetate. The organic layers were combined, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo to give a crude residue which was purified by flash column chromatography (1:1 AcOEt/heptane) to give 1-benzyl-4-(2-methoxyethyl)-piperidine-4-carboxylic acid ethyl ester (5.2 g, 84%) as a brown oil. MS (ESI): 306.3 (MH+).

Workup

  1. stirringstirring
  2. waitwas continued for a further 3 hr
  3. temperatureto warm to room temperature
  4. stirringstirring
  5. waitwas continued overnight
  6. customThe reaction mixture was quenched with water
  7. concentrationconcentrated in vacuo
  8. customto give a brown residue which
  9. extractionextracted 1N HCl
  10. extractionextracted with ethyl acetate
  11. washwashed with brine
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customto give a crude residue which
  16. customwas purified by flash column chromatography (1:1 AcOEt/heptane)

Sources & evidence

ORD record
ord-1d797cfbe229431c86390607ab1c5112
Source dataset
uspto-grants-2012_12
Patent number
US08329904B2

Reaction notes

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