Hydrochloric Acid → 2,2,6,6-Tetramethylpiperidin-4-yl heptanoate

HRID 874696Notes

Reaction equation

HRID 874696 reaction equation
C[N+](C1C=CC=C(O)C=1)(C)C.[I-].[CH3:13][C:14]1([CH3:23])[CH2:19][CH:18]([OH:20])[CH2:17][C:16]([CH3:22])([CH3:21])[NH:15]1.[C:24](OC)(=[O:31])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30].C(=O)([O-])[O-].[K+].[K+].N#N.[ClH:42]>CN(C)C=O.CO>[CH3:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][C:24]([O:20][CH:18]1[CH2:17][C:16]([CH3:22])([CH3:21])[NH:15][C:14]([CH3:23])([CH3:13])[CH2:19]1)=[O:31].[ClH:42]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 947NitrogenHCID 7826Methyl heptanoateHCID 11430Potassium CarbonateHCID 172503-Hydroxyphenyltrimethylammonium iodideHCID 754714-Hydroxy-2,2,6,6-tetramethylpiperidine

Product 1

HCID 160790142,2,6,6-Tetramethylpiperidin-4-yl heptanoateYield 41%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

TMPH Synthesis. To a mixture of 2,2,6,6-tetramethyl-4-piperidinol (472 mg, 3.0 mmol) and methyl heptanoate (476 mg, 3.3 mmol) in 3.0 mL of dimethyl formamide was added 250 mg of powdered potassium carbonate. The resulting mixture was heated at 145˜155° C. for 64 hours under a gentle stream of N2. After cooling, the reaction mixture was partitioned between water and hexanes. The organic layer was separated, washed with water (2×) and brine, then dried over anhydrous MgSO4 and evaporated to afford the crude product as an oil. The oil was dissolved in MeOH and was then treated with 2 equivalents of conc. HCl. The solvent was removed in vacuo, and the residue was then treated with diethyl ether. The resulting solids were removed by filtration. The ethereal filtrate was concentrated in vacuo and triturated with hexane to afford 380 mg (41%) of TMPH hydrochloride. It was recrystallized from boiling ethyl acetate/hexane to afford short colorless needles, mp 113-115° C. FAB-HRMS: calculated (C16H32NO2): 270.2433 found: 270.2435.

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between water and hexanes
  3. customThe organic layer was separated
  4. washwashed with water (2×) and brine
  5. dry with materialdried over anhydrous MgSO4
  6. customevaporated
  7. customto afford the crude product as an oil
  8. customThe solvent was removed in vacuo
  9. additionthe residue was then treated with diethyl ether
  10. customThe resulting solids were removed by filtration
  11. concentrationThe ethereal filtrate was concentrated in vacuo
  12. customtriturated with hexane

Sources & evidence

ORD record
ord-e6daf2a846514a8e8ae12935b9363870
Source dataset
uspto-grants-2015_03
Patent number
US08980923B2

Reaction notes

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