Dimethylformamide → N-hydroxy-1-[4-methoxybenzenesulfonyl]-pyrrolidine-2(S)-carboxamide

HRID 264289

Reaction equation

HRID 264289 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]2[CH2:16][CH2:15][CH2:14][C@@H:13]2[C:17]([OH:19])=O)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.Cl.[NH2:32][OH:33].C(N(CC)CC)C>C(Cl)Cl.O1CCCC1.O>[OH:33][NH:32][C:17]([C@@H:13]1[CH2:14][CH2:15][CH2:16][N:12]1[S:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)(=[O:11])=[O:10])=[O:19]

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 443297Hydroxyamine hydrochlorideHCID 7449021-[(4-Methoxyphenyl)sulfonyl]-D-proline

Product 1

HCID 11022968N-hydroxy-1-[4-methoxybenzenesulfonyl]-pyrrolidine-2(S)-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

1-[4-Methoxybenzenesulfonyl]-pyrrolidine-2(R)-carboxylic acid (1.12 g, 3.93 mmol) is dissolved in methylene chloride (40.0 mL). To this solution is added oxalyl chloride (0.69 mL, 7.85 mmol) and dimethylformamide (0.30 mL, 3.93 mmol), and the reaction is stirred at room temperature for 30 minutes. Meanwhile, in a separate flask, hydroxylamine hydrochloride (1.1 g, 15.7 mmol) and triethylamine (3.3 mL, 23.5 mmol) are stirred in tetrahydrofuran (20.0 mL) and water (4.0 mL) at 0° C. for 15 minutes. After 30 minutes, the methylene chloride solution is added in one portion to the second flask, and the combined contents are stirred overnight as the flask gradually warms up to room temperature. The reaction is then diluted with acidic water (pH=~3), and extracted several times with ethyl acetate. The combined organic layers are dried (MgSO4), and the solvent is evaporated. The product is purified by silica gel chromatography (50% ethyl acetate/hexane) to give N-hydroxy-1 -[4-methoxybenzenesulfonyl]-pyrrolidine-2(S)-carboxamide, m.p. 163.5°-165.5° C.

Workup

  1. waitAfter 30 minutes
  2. stirringthe combined contents are stirred overnight as the flask
  3. customgradually warms up to room temperature
  4. extractionextracted several times with ethyl acetate
  5. dry with materialThe combined organic layers are dried (MgSO4)
  6. customthe solvent is evaporated
  7. customThe product is purified by silica gel chromatography (50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a4ac08fd061041b2b96b5d4eadf86961
Source dataset
uspto-grants-1997_07
Patent number
US05646167

Linked notes

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