Dimethylformamide → (S)-1-[(S)-1-(2,3-Dihydro-benzo[1,4]dioxin-2-yl)methyl]-3-methyl-piperidine-3-carboxylic acid ethyl ester

HRID 453826Notes

Reaction equation

HRID 453826 reaction equation
[CH2:1]([O:3][C:4]([C@@:6]1([CH3:12])[CH2:11][CH2:10][CH2:9][NH:8][CH2:7]1)=[O:5])[CH3:2].[O:13]1[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[O:16][CH2:15][C@@H:14]1[CH2:23]OS(C1C=CC(C)=CC=1)(=O)=O.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH2:1]([O:3][C:4]([C@@:6]1([CH3:12])[CH2:11][CH2:10][CH2:9][N:8]([CH2:23][C@@H:14]2[O:13][C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[O:16][CH2:15]2)[CH2:7]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 7101148(R)-(2,3-Dihydrobenzo[b][1,4]dioxin-2-yl)methyl 4-methylbenzenesulfonateHCID 23389262(S)-Ethyl 3-methylpiperidine-3-carboxylate

Product 1

HCID 25176453(S)-1-[(S)-1-(2,3-Dihydro-benzo[1,4]dioxin-2-yl)methyl]-3-methyl-piperidine-3-carboxylic acid ethyl esterYield 80.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-ethyl-3-methylpiperidine-3-carboxylate (7.23 g, 42.2 mmol), Toluene-4-sulfonic acid (R)-1-(2,3-dihydro-benzo[1,4]dioxin-2-yl)methyl ester (15.0 g, 44.3 mmol), potassium carbonate (6.42 g, 46.4 mmol) and N,N-dimethyl formamide (50 ml) was heated to 120° C. After 4 hours the reaction mixture was cooled down, water (35 ml) was added and the mixture was extracted twice with ethyl acetate. The combined ethyl acetate layers were evaporated to dryness. Toluene (35 ml) was added to the evaporation residue and the mixture was extracted twice with 1M HCl. The combined acidic water layers were made basic with aq NaOH. The basic water layer was extracted twice with ethyl acetate and the combined ethyl acetate layers were evaporated to dryness to yield 10.8 g (76%) of the title compound.

Workup

  1. temperatureAfter 4 hours the reaction mixture was cooled down
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. customThe combined ethyl acetate layers were evaporated to dryness
  4. additionToluene (35 ml) was added to the evaporation residue
  5. extractionthe mixture was extracted twice with 1M HCl
  6. extractionThe basic water layer was extracted twice with ethyl acetate
  7. customthe combined ethyl acetate layers were evaporated to dryness

Sources & evidence

ORD record
ord-36991508708a4bae930df5efab187451
Source dataset
uspto-grants-2013_07
Patent number
US08492549B2

Reaction notes

Loading…