Dimethyl Sulfoxide → HCID 67366301, compound

HRID 1753196Notes

Reaction equation

HRID 1753196 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][S:8]([CH3:10])=O.[F:11][C:12]1[CH:17]=[CH:16][C:15]([CH:18]([OH:29])[CH2:19][N:20]2[C:24]([CH3:25])=[CH:23][CH:22]=[C:21]2[C:26]([OH:28])=[O:27])=[CH:14][CH:13]=1.C(N(CC)CC)C>C(Cl)Cl>[F:11][C:12]1[CH:13]=[CH:14][C:15]([C:18](=[O:29])[CH2:19][N:20]2[C:24]([CH3:25])=[CH:23][CH:22]=[C:21]2[C:26]([O:28][CH2:7][S:8][CH3:10])=[O:27])=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 67367711HCID 67367711, compound

Product 1

HCID 67366301HCID 67366301, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of oxalyl chloride (0.3 mL, 3.5 mmol) in CH2Cl2 (0.5 mL) was added drop-wise to a solution of DMSO (0.34 mL, 4.8 mmol) in CH2Cl2 (1.5 mL) at −65° C. and stirred for 10 min. The resultant solution was added to a suspension of 1-[2-(4-fluorophenyl)-2-hydroxyethyl]-5-methyl-1H-pyrrole-2-carboxylic acid (211 mg, 0.8 mmol) in CH2Cl2 (10 mL) at −65° C. The resultant suspension was stirred at −65° C. for 15 min, then triethylamine (1.12 mL, 8.0 mmol) was added drop-wise. Once the addition was complete the reaction mixture was allowed to warm to room temperature and stirred for 2 hours. The reaction was then quenched by the addition of CH2Cl2 (50 mL) and water (10 mL), the organic layer was separated and the aqueous extracted with further CH2Cl2 (10 mL). The organic layers were combined and washed with brine, dried (MgSO4), filtered and concentrated in vacuo to give a brown solid. The solid was purified by flash column chromatography (Biotage SP4, 40 g cartridge, hexane 1 CV, 0-50% EtOAc/hexanes 10 CV) to give (methylsulfanyl)methyl 1-[2-(4-fluorophenyl)-2-oxoethyl]-5-methyl-1H-pyrrole-2-carboxylate as a off-white solid (162 mg, 62%). 1H NMR (400 MHz, CDCl3): δ 2.19 (s, 3H), 2.22 (s, 3H), 5.19 (s, 2H), 5.76 (s, 2H), 6.06 (dd, 1H, J 3.9, 0.7 Hz), 7.06 (d, 1H, J 3.9 Hz), 7.13-7.24 (m, 2H), 8.06 (dd, 2H, J 9.0, 5.3 Hz). ESI-MI m/z [M+H]+ 321.80.

Workup

  1. additionOnce the addition
  2. stirringstirred for 2 hours
  3. customThe reaction was then quenched by the addition of CH2Cl2 (50 mL) and water (10 mL)
  4. customthe organic layer was separated
  5. extractionthe aqueous extracted with further CH2Cl2 (10 mL)
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a brown solid
  11. customThe solid was purified by flash column chromatography (Biotage SP4, 40 g cartridge, hexane 1 CV, 0-50% EtOAc/hexanes 10 CV)

Sources & evidence

ORD record
ord-e7a856c0815d45f2bf8e0611e09afe68
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

Loading…