Hydrochloric Acid → HCID 66580238, compound

HRID 2368814Notes

Reaction equation

HRID 2368814 reaction equation
CS(C)=O.[OH:5][CH:6]1[CH2:29][CH2:28][C:9]2([C:13](=[O:14])[N:12]([C:15]3[CH:16]=[N:17][C:18]([O:21][C@@H:22]([CH3:27])[C:23]([F:26])([F:25])[F:24])=[CH:19][CH:20]=3)[CH2:11][CH2:10]2)[CH2:8][CH2:7]1.C(Cl)(=O)C(Cl)=O.Cl>ClCCl.C(N(CC)CC)C>[F:26][C:23]([F:24])([F:25])[C@H:22]([CH3:27])[O:21][C:18]1[N:17]=[CH:16][C:15]([N:12]2[CH2:11][CH2:10][C:9]3([CH2:8][CH2:7][C:6](=[O:5])[CH2:29][CH2:28]3)[C:13]2=[O:14])=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 679Dimethyl SulfoxideHCID 65578Oxalyl chlorideHCID 66580324HCID 66580324, compound

Product 1

HCID 66580238HCID 66580238, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-78 °C

Procedure

DMSO (16.3 ml) was added dropwise over a period of 5 minutes to a solution of 8-hydroxy-2-[6-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-pyridin-3-yl]-2-aza-spiro[4.5]decan-1-one (39.3 g) in dichloromethane (400 ml) that was cooled down to −78° C. in a CO2/acetone-bath. After 5 minutes, oxalylchloride (15.6 ml) was added dropwise over a period of 15 minutes and stirring was continued for 30 minutes at −78° C. Then, triethylamine (42.7 ml) was added dropwise over a period of 15 minutes to the reaction mixture and after 5 minutes, the mixture was allowed to warm to 20° C. and stirred further 2 h at R.T. The reaction mixture was poured into ice/water and was acidified with 2M aqueous HCl solution to pH 3. The aqueous phase was extracted two times with dichloromethane and the combined organic layers were washed with brine, dried over Na2SO4 and filtered. The solvent was evaporated and the residue was purified by flash chromatography (silica gel, gradient 20% to 60 of AcOEt in hexane) to give the title compound as an off white solid (23.96 g). MS (m/e): 357.2 (MO.

Workup

  1. waitwas continued for 30 minutes at −78° C
  2. temperatureto warm to 20° C.
  3. stirringstirred further 2 h at R.T
  4. extractionThe aqueous phase was extracted two times with dichloromethane
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customThe solvent was evaporated
  9. customthe residue was purified by flash chromatography (silica gel, gradient 20% to 60 of AcOEt in hexane)

Sources & evidence

ORD record
ord-f0a91f3f06644147aa7869e417c43c78
Source dataset
uspto-grants-2014_04
Patent number
US08703807B2

Reaction notes

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