Dimethyl Sulfoxide → HCID 13192293, compound

HRID 1784797Notes

Reaction equation

HRID 1784797 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[CH2:11]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C@@H:24]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([CH3:34])[C:29]=2[CH3:35])[C@H:23]([OH:36])[CH2:22]1)=[O:20])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(N(CC)CC)C>ClCCl.O>[CH3:35][C:29]1[C:30]([CH3:34])=[CH:31][CH:32]=[CH:33][C:28]=1[O:27][CH:24]1[CH2:25][CH2:26][N:21]([C:19]([O:18][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:20])[CH2:22][C:23]1=[O:36]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 68894799HCID 68894799, compound

Product 1

HCID 13192293HCID 13192293, compoundYield 99.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-60 °C

Procedure

A solution of oxalyl chloride (3.5 ml, 40 mmol, 1.1 eq.) in dichloromethane (350 ml) was cooled to −60° C. (internal temp.) and treated drop-wise with dimethyl sulfoxide (5.18 ml, 73.0 mmol, 2 eq.). On completion of addition the reaction mixture was stirred at −60° C. for 5 min. before drop-wise addition of a solution of trans-benzyl-4-(2,3-dimethylphenoxy)-3-hydroxypiperidine-1-carboxylate (13.0 g, 36.5 mmol) in dichloromethane (50 ml). After 30 min. triethylamine (15.5 ml, 110 mmol, 3.0 eq.) was added drop-wise and the solution stirred at −60° C. for 10 min, before allowing the mixture to warm slowly to room temperature. After 18 h. the reaction mixture was diluted with water (400 ml) and the resultant biphasic system separated. The aqueous layer was extracted with dichloromethane (400 ml). Combined organics were washed with aqueous hydrochloric acid (200 ml, 0.1N), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to furnish benzyl 4-(2,3-dimethylphenoxy)-3-oxopiperidine-1-carboxylate as a pale yellow amorphous solid (12.8 g, 99%).

Workup

  1. additionOn completion of addition the reaction mixture
  2. temperatureto warm slowly to room temperature
  3. customthe resultant biphasic system separated
  4. extractionThe aqueous layer was extracted with dichloromethane (400 ml)
  5. washCombined organics were washed with aqueous hydrochloric acid (200 ml, 0.1N)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-396c21b53fe14c60a2218777356825ad
Source dataset
uspto-grants-2009_03
Patent number
US07504419B2

Reaction notes

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