Dimethyl Sulfoxide → {(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}acetaldehyde

HRID 1039046Notes

Reaction equation

HRID 1039046 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[CH:13]=[N:14][C:15]([N:18]2[CH2:23][CH2:22][CH:21]([C@H:24]3[CH2:26][C@H:25]3[CH2:27][CH2:28][OH:29])[CH2:20][CH2:19]2)=[N:16][CH:17]=1>C(Cl)Cl.O>[Cl:11][C:12]1[CH:13]=[N:14][C:15]([N:18]2[CH2:23][CH2:22][CH:21]([C@H:24]3[CH2:26][C@H:25]3[CH2:27][CH:28]=[O:29])[CH2:20][CH2:19]2)=[N:16][CH:17]=1

Participants

6

Reactant 3

HCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 581286112-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol

Product 1

HCID 86666140{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}acetaldehyde

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-50 °C

Procedure

A flame dried flask was charged with DCM (20 ml) and oxalyl chloride (0.90 g, 0.62 mmol) under N2. The vessel was cooled to −50° C. in an acetorntrile:dry ice bath. DMSO (1.1 g, 14.2 mmol) was added drop wise after which the solution was stirred for 2 minutes. A solution of 2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol from step 6 of Example 1 (1 g, 3.55 mmol) in DCM (15 ml) was added drop wise and the mixture was stirred for 15 minutes. TEA (2.88 g, 28.4 mmol) was added, the mixture stirred for 15 minutes at −50° C. and then allowed to warm to RT for 1 hour. Water (15 ml) was then added drop wise, the mixture diluted with an additional 50 ml water. The mixture was then place in a separatory funnel, shaken and the layers separated. The aqueous phase was extracted with DCM (2×35 ml), the organic fractions combined, washed with brine, dried over Na2SO4, filtered, and the volatiles removed in vacuum strip. The product was purified by chromatography on SiO2 eluting with 30% acetone:hexanes. LRMS calc: 279.11; obs: 280.05 (M+1).

Workup

  1. customA flame dried flask
  2. stirringthe mixture was stirred for 15 minutes
  3. stirringthe mixture stirred for 15 minutes at −50° C.
  4. temperatureto warm to RT for 1 hour
  5. stirringplace in a separatory funnel, shaken
  6. customthe layers separated
  7. extractionThe aqueous phase was extracted with DCM (2×35 ml)
  8. washwashed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customthe volatiles removed in vacuum strip
  12. customThe product was purified by chromatography on SiO2 eluting with 30% acetone

Sources & evidence

ORD record
ord-edad75e98d604cd8a50753600ddc00a0
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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