Oxalyl chloride → HCID 118383383, compound

HRID 2202758Notes

Reaction equation

HRID 2202758 reaction equation
C(Cl)(=O)C(Cl)=O.[CH2:7]([O:9][C:10]([C@H:12]1[CH2:17][CH2:16][C@H:15]([N:18]2[C:22]([C:23]([F:26])([F:25])[F:24])=[C:21]([C:27]([OH:29])=O)[CH:20]=[N:19]2)[CH2:14][C:13]1([CH3:31])[CH3:30])=[O:11])[CH3:8].[Cl:32][C:33]1[CH:34]=[N:35][CH:36]=[C:37]([Cl:55])[C:38]=1[CH:39]([O:47][Si](CC)(CC)CC)[CH2:40][NH:41][CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44].CCN(C(C)C)C(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>CN(C=O)C.C1COCC1.C(Cl)Cl>[Cl:32][C:33]1[CH:34]=[N:35][CH:36]=[C:37]([Cl:55])[C:38]=1[C:39](=[O:47])[CH2:40][N:41]([CH2:42][C:43]([CH3:44])([CH3:46])[CH3:45])[C:27]([C:21]1[CH:20]=[N:19][N:18]([C@H:15]2[CH2:16][CH2:17][C@H:12]([C:10]([O:9][CH2:7][CH3:8])=[O:11])[C:13]([CH3:30])([CH3:31])[CH2:14]2)[C:22]=1[C:23]([F:24])([F:25])[F:26])=[O:29]

Participants

10

Reactant 6

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 159087TriacetoxyperiodinaneHCID 2724141Tetrabutylammonium FluorideHCID 118383070HCID 118383070, compoundHCID 123315860HCID 123315860, compound

Product 1

HCID 118383383HCID 118383383, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Oxalyl chloride (64 μL, 0.72 mmol) and DMF (1 drop) were added sequentially to a stirring solution of trans-1-(4-(ethoxycarbonyl)-3,3-dimethylcyclohexyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (0.20 g, 0.55 mmol; racemic mixture) and DCM (5.5 mL). After stirring for 2 h, the reaction mixture was concentrated under reduced pressure. The residue was dissolved with THF (4.5 mL), and then a solution of N-(2-(3,5-dichloropyridin-4-yl)-2-((triethylsilyl)oxy)ethyl)-2,2-dimethylpropan-1-amine (0.22 g, 0.55 mmol) and THF (1.0 mL) was added followed by DIPEA (0.29 mL, 1.7 mmol). After stirring for 30 min, TBAF (1.7 mL of a 1.0 M solution with THF, 1.7 mmol) was added. After stirring for 1 h, the reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3, the layers were separated, the organic material washed sequentially with saturated aqueous NaHCO3 (2×) and brine, dried (Na2SO4), filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved with DCM (5.5 mL) and the resulting solution was treated with Dess-Martin periodinane (0.26 g, 0.60 mmol). After stirring for 10 min, the reaction mixture was concentrated under reduced pressure, the residue was partitioned between THF-EtOAc (1:1 vol/vol) and saturated aqueous NaHCO3, the layers were separated, the organic material was washed sequentially with saturated aqueous NaHCO3 and brine, dried (Na2SO4), filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved with DCM, silica gel (1.0 g) was added to the solution, and the volatiles were removed under reduced pressure. The residue was subjected to flash chromatography on silica gel (gradient elution; 9:1 to 4:1 hexane-EtOAc) to give ethyl trans-4-(4-((2-(3,5-dichloro-4-pyridinyl)-2-oxoethyl)(2,2-dimethylpropyl)carbamoyl)-5-(trifluoromethyl)-1H-pyrazol-1-yl)-2,2-dimethylcyclohexanecarboxylate (0.27 g, 80% overall yield; racemic mixture) as a colorless solid.

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved with THF (4.5 mL)
  3. stirringAfter stirring for 30 min
  4. stirringAfter stirring for 1 h
  5. customthe reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3
  6. customthe layers were separated
  7. washthe organic material washed sequentially with saturated aqueous NaHCO3 (2×) and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. dissolutionThe residue was dissolved with DCM (5.5 mL)
  12. stirringAfter stirring for 10 min
  13. concentrationthe reaction mixture was concentrated under reduced pressure
  14. customthe residue was partitioned between THF-EtOAc (1:1 vol/vol) and saturated aqueous NaHCO3
  15. customthe layers were separated
  16. washthe organic material was washed sequentially with saturated aqueous NaHCO3 and brine
  17. dry with materialdried (Na2SO4)
  18. filtrationfiltered
  19. concentrationthe filtrate was concentrated under reduced pressure
  20. dissolutionThe residue was dissolved with DCM, silica gel (1.0 g)
  21. additionwas added to the solution
  22. customthe volatiles were removed under reduced pressure

Sources & evidence

ORD record
ord-c43a0eb33d3f4f26b0ba5ef7cb0c0c49
Source dataset
uspto-grants-2016_06
Patent number
US09365522B2

Reaction notes

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