Diisopropylamine → HCID 67037408, compound

HRID 1777346Notes

Reaction equation

HRID 1777346 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH2:13]([O:15][C:16]([CH:18]1[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]1)=[O:17])[CH3:14].Cl[CH2:32][O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.[Cl-].[NH4+]>O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O>[CH2:13]([O:15][C:16]([C:18]1([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:20][CH2:19]1)=[O:17])[CH3:14]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 137983Benzyl chloromethyl etherHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylateHCID 178418339Butyllithium

Product 1

HCID 67037408HCID 67037408, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 12679HexamethylphosphoramideSolvent

Conditions

Temperature
-70 °C

Procedure

n-Butyllithium (15% solution in n-hexane; 9.5 mL, 0.022 mol) is added to a stirred solution of diisopropyl amine (3.1 mL, 0.022 mol) in tetrahydrofuran (15 mL) at −70° C. under an atmosphere of nitrogen and stirred for 30 minutes. A solution of piperidine-1,4-dicarboxylic acid-1-tert-butyl ester-4-ethyl ester (3 g, 0.012 mol) in tetrahydrofuran (10 mL) is introduced at −70° C. Hexamethyl phosphoramide (4.8 mL) is added and reaction mixture is allowed to stir till the temperature reaches at −45° C. Reaction mixture again cooled to −70° C., benzyl chloromethyl ether (5 mL, 0.035 mol) is added and stirred for 1 hour. Saturated aqueous solution of ammonium chloride (30 mL) is added slowly into the reaction mixture at −30° C. and stirred for 10 minutes. It is extracted with ethyl acetate (2×20 mL). Combined organic layer is dried over sodium sulfate. Removal of solvent under reduced pressure gives a viscous liquid which is purified by column chromatography (silica gel 230-400, toluene:ethyl acetate, 23:2 to furnish 4-benzyloxymethylpiperidine-1,4-dicarboxylic acid-1-tert-butyl ester-4-ethyl ester.

Workup

  1. customreaction mixture
  2. stirringto stir till the temperature
  3. customreaches at −45° C
  4. customReaction mixture
  5. stirringstirred for 1 hour
  6. stirringstirred for 10 minutes
  7. extractionIt is extracted with ethyl acetate (2×20 mL)
  8. dry with materialCombined organic layer is dried over sodium sulfate
  9. customRemoval of solvent under reduced pressure
  10. customgives a viscous liquid which
  11. customis purified by column chromatography (silica gel 230-400, toluene

Sources & evidence

ORD record
ord-06996500aa3640248a26b9ee55d47278
Source dataset
uspto-grants-2016_02
Patent number
US09266867B2

Reaction notes

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