Dimethylformamide → (2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-4-methylpentanamide

HRID 742023Notes

Reaction equation

HRID 742023 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([N:12]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@H:13]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:14](O)=[O:15])(=[O:11])=[O:10])=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.Cl.[NH2:40][OH:41].C(N(CC)CC)C>C(Cl)Cl.O1CCCC1.O>[OH:41][NH:40][C:14](=[O:15])[C@H:13]([N:12]([S:9]([C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)(=[O:11])=[O:10])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:17][CH:18]([CH3:20])[CH3:19]

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 443297Hydroxyamine hydrochlorideHCID 117948032(R)-[[4methoxybenzenesulfonyl](benzyl)amino]-4-methylpentanoic acid

Product 1

HCID 10787514(2R)-2-[benzyl(4-methoxybenzene)sulfonamido]-N-hydroxy-4-methylpentanamide

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

2(R)-[[4-Methoxybenzenesulfonyl](benzyl)amino]-4-methylpentanoic acid (4.38 g, 11.2 mmol) is dissolved in methylene chloride (56.0 mL). To this solution is added oxalyl chloride (1.95 mL, 22.4 mmol) and dimethylformamide (0.86 mL, 11.2 mmol), and the reaction is stirred at room temperature for 90 minutes. Meanwhile, in a separate flask, hydroxylamine hydrochloride (3.11 g, 44.8 mmol) and triethylamine (9.36 mL, 67.1 mmol) are stirred in tetrahydrofuran (50.0 mL) and water (3.5 mL) at 0° C. for 15 minutes. After 90 minutes, the methylene chloride solution is added in one portion to the second flask, and the combined contents are stirred for three days 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 (Na2SO4), and the solvent is evaporated. The product is purified by silica gel chromatography (1% methanol/methylene chloride) to give N-hydroxy-2(R)-[[4-methoxybenzenesulfonyl](benzyl)amino]-4-methylpentanamide, m.p. 48°-52° C.

Workup

  1. waitAfter 90 minutes
  2. stirringthe combined contents are stirred for three days 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 (Na2SO4)
  6. customthe solvent is evaporated
  7. customThe product is purified by silica gel chromatography (1% methanol/methylene chloride)

Sources & evidence

ORD record
ord-d57921a4dbab420b8b86f01d4afa8715
Source dataset
uspto-grants-1996_09
Patent number
US05552419

Reaction notes

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