Oxalyl chloride → HCID 178456050, compound

HRID 1802435Notes

Reaction equation

HRID 1802435 reaction equation
[CH3:1][C@@H:2]([S:5]([C:8]([CH3:13])([CH3:12])[C:9]([OH:11])=O)(=[O:7])=[O:6])[CH2:3][CH3:4].C(Cl)(=O)C(Cl)=O.C(N(CC)C(C)C)(C)C.[CH3:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([C:37]2[NH:38][C:39]([NH2:42])=[N:40][N:41]=2)=[CH:33][CH:32]=1>CN(C=O)C.C(Cl)Cl.C1COCC1>[CH3:1][C@@H:2]([S:5]([C:8]([CH3:13])([CH3:12])[C:9]([NH:42][C:39]1[NH:38][C:37]([C:34]2[CH:35]=[CH:36][C:31]([O:30][CH3:29])=[CH:32][CH:33]=2)=[N:41][N:40]=1)=[O:11])(=[O:6])=[O:7])[CH2:3][CH3:4]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 59267939HCID 59267939, compoundHCID 178489124HCID 178489124, compound

Product 1

HCID 178456050HCID 178456050, compoundYield 19.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

Activation of 0.5 g (2.40 mmol) of 2-[(2R)-butane-2-sulfonyl]-2-methyl-propionic acid as the corresponding acid chloride is achieved by treatment with oxalyl chloride (0.41 mL, 4.80 mmol), DMF (1 drop) in DCM (10 mL) at room temperature for 18 h. The reaction is concentrated under reduced pressure and excess oxalyl chloride is removed by azeotrope distillation with toluene (3×5 mL) under reduced pressure. The crude acid chloride is dissolved in THF (5 mL) and added to a solution of N,N-diisopropylethylamine (0.84 mL, 4.80 mmol) and 0.3 g (1.58 mmol) of 5-(4-methoxy-phenyl)-4H-[1,2,4]triazol-3-ylamine in THF (5 mL). After complete addition the reaction is heated to 80° C. for 48 h. The reaction is cooled to room temperature and the solvent is removed under reduced pressure. The residue is dissolved in DCM (20 mL) and washed with saturated aqueous NaHCO3 solution (20 mL). The aqueous layer is back-extracted with DCM (2×20 mL). The combined organic layers are dried over Na2SO4, filtered and the filtrate is concentrated under reduced pressure. The residue is purified by column chromatography (silica, eluent: heptanes, 0-50% ethyl acetate) to yield 0.119 g of 2-[(2R)-butane-2-sulfonyl]-N-[5-(4-methoxyphenyl)-4H-1,2,4-triazol-3-yl]-2-methylpropanamide. Yield: 13%; ES-MS: m/z 381 [M+H]

Workup

  1. concentrationThe reaction is concentrated under reduced pressure and excess oxalyl chloride
  2. customis removed by azeotrope distillation with toluene (3×5 mL) under reduced pressure
  3. dissolutionThe crude acid chloride is dissolved in THF (5 mL)
  4. additionAfter complete addition the reaction
  5. temperatureThe reaction is cooled to room temperature
  6. customthe solvent is removed under reduced pressure
  7. dissolutionThe residue is dissolved in DCM (20 mL)
  8. washwashed with saturated aqueous NaHCO3 solution (20 mL)
  9. extractionThe aqueous layer is back-extracted with DCM (2×20 mL)
  10. dry with materialThe combined organic layers are dried over Na2SO4
  11. filtrationfiltered
  12. concentrationthe filtrate is concentrated under reduced pressure
  13. customThe residue is purified by column chromatography (silica, eluent: heptanes, 0-50% ethyl acetate)

Sources & evidence

ORD record
ord-2c20c76fd47547849ca41312e16566f1
Source dataset
uspto-grants-2013_01
Patent number
US08349871B2

Reaction notes

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