4-Hydroxy-2,2,6,6-tetramethylpiperidine → 2,2,6,6-Tetramethylpiperidin-4-yl 6-(octanoylamino)hexanoate

HRID 2298442Notes

Reaction equation

HRID 2298442 reaction equation
[C:1]([NH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH3:20][C:21]1([CH3:30])[CH2:26]C(O)[CH2:24][C:23]([CH3:29])([CH3:28])[NH:22]1>C(O[Sn](CCCC)(CCCC)O[Sn](OC(=O)C)(CCCC)CCCC)(=O)C.C1(C)C=CC=CC=1>[C:1]([NH:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH:19]1[CH2:24][C:23]([CH3:29])([CH3:28])[NH:22][C:21]([CH3:30])([CH3:26])[CH2:20]1)=[O:17])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]

Participants

5

Reactant 2

HCID 754714-Hydroxy-2,2,6,6-tetramethylpiperidineHCID 11747683Methyl 6-(octanoylamino)hexanoate

Product 1

HCID 121493962,2,6,6-Tetramethylpiperidin-4-yl 6-(octanoylamino)hexanoateYield 90%

Reagents, catalysts & solvents 2

HCID 16682981Acetic acid, 1,1'-(1,1,3,3-tetrabutyl-1,3-distannoxanediyl) esterCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A 250 mL single-necked reaction flask was equipped with a magnetic stirrer and a Dean-Stark trap fitted with a condenser and nitrogen inlet/outlet. To this flask was charged 6.1 g (22.5 mmol) of compound D, 5.29 g (33.7 mmol) of 2,2,6,6-tetramethyl-4-piperidinol, and 150 mL of toluene. Under a slow nitrogen flow, 8 mL of toluene was distilled off and the trap drained. After lowering the heat source and allowing the mixture to cool to 110° C., 0.17 g (0.28 mmol) of 1,3-diacetoxy-1,1,3,3-tetrabutyldistannoxane was added and the heat source raised. Another 100 mL of toluene was slowly distilled off over 16 hours and the resulting mixture was cooled to room temperature and diluted with methylene chloride. The organic solution was washed with water to remove excess amino alcohol and dried over anhydrous sodium carbonate. Filtration and removal of solvent under reduced pressure followed by further solvent removal in vacuo (<1 mm) at 60° C. gave 8.0 g (90%) of Compound VI as a light brown wax. The structure of the material was confirmed by 1H NMR analysis. 1H NMR (CDCl3): δ 5.60 (m, 1H, NHCO—); 5.18 (m, 1H, R2CHOCO—); 3.25 (dt, 2H, —CH2—NH—); 2.28 (t, 2H, —CH2COO—); 2.16 (t, 2H, —CH2CONH—); 1.95-1.10 (m, 20H, CH2(CH2)3CH2, CH2(CH2)5, CH2CH2C(CH3)2); 1.20 (d, 12H, CH2C(CH3)2; 0.88 (t, 3H, —CH2CH3).

Workup

  1. customA 250 mL single-necked reaction flask was equipped with a magnetic stirrer
  2. customa Dean-Stark trap fitted with a condenser and nitrogen inlet/outlet
  3. distillationUnder a slow nitrogen flow, 8 mL of toluene was distilled off
  4. temperaturethe heat source raised
  5. distillationAnother 100 mL of toluene was slowly distilled off over 16 hours
  6. temperaturethe resulting mixture was cooled to room temperature
  7. additiondiluted with methylene chloride
  8. washThe organic solution was washed with water
  9. customto remove excess amino alcohol
  10. dry with materialdried over anhydrous sodium carbonate
  11. filtrationFiltration and removal of solvent under reduced pressure
  12. customfollowed by further solvent removal in vacuo (<1 mm) at 60° C.

Sources & evidence

ORD record
ord-1ccca0ac12c447e6acca4f487bc5aca3
Source dataset
uspto-grants-2002_12
Patent number
US06492521B2

Reaction notes

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