Acetic Acid → HCID 86641102, compound

HRID 1809607Notes

Reaction equation

HRID 1809607 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]([N:16]1[CH2:21][CH2:20][C:19]([CH3:27])([C:22]([O:24]CC)=O)[CH2:18][CH2:17]1)([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].[Cl:28][CH2:29]I.C(O)(=O)C>C1COCC1>[Cl:28][CH2:29][C:22]([C:19]1([CH3:27])[CH2:18][CH2:17][N:16]([C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[CH2:21][CH2:20]1)=[O:24]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 11644ChloroiodomethaneHCID 2724682Lithium diisopropylamideHCID 162182761-tert-Butyl 4-ethyl 4-methylpiperidine-1,4-dicarboxylate

Product 1

HCID 86641102HCID 86641102, compoundYield 44.92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Lithium diisopropylamide (30.9 mL, 46.4 mmol) was added dropwise to a solution containing ethyl N-Boc-4-methylpiperidine-4-carboxylate (2.52 g, 9.28 mmol), and chloroiodomethane (6.55 g, 37.1 mmol) in THF (100 mL) at −78° C. over 30 minutes. After addition, the reaction was stirred for 10 minutes, and then a solution of acetic acid (5 mL) in THF (45 mL) was added while keeping reaction mixture below −65° C. The reaction was stirred for an additional 10 minutes and partitioned between ethyl acetate and brine, washed with saturated bicarbonate, concentrated and purified by silica gel (10%-20% ethyl acetate in hexanes) to afford tert-butyl 4-(2-chloroacetyl)-4-methylpiperidine-1-carboxylate (1.15 g, 44.92% yield).

Workup

  1. additionAfter addition
  2. customreaction mixture below −65° C
  3. stirringThe reaction was stirred for an additional 10 minutes
  4. custompartitioned between ethyl acetate and brine
  5. washwashed with saturated bicarbonate
  6. concentrationconcentrated
  7. custompurified by silica gel (10%-20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-75f6867d3db840e0b89681330303bd6a
Source dataset
uspto-grants-2013_01
Patent number
US08362037B2

Reaction notes

Loading…