Dimethylformamide → (+/-)-4-(4-Bromophenyl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamide

HRID 533502Notes

Reaction equation

HRID 533502 reaction equation
C(Cl)(=O)C(Cl)=O.[Br:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]([CH3:24])([S:20]([CH3:23])(=[O:22])=[O:21])[C:17](O)=[O:18])=[CH:10][CH:9]=1.CN(C=O)C.[Si]([O:34][NH2:35])(C)(C)C>C(Cl)Cl>[Br:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16]([CH3:24])([S:20]([CH3:23])(=[O:22])=[O:21])[C:17]([NH:35][OH:34])=[O:18])=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 66577906(+/-)-4-(4-Bromophenyl)-2-methyl-2-(methylsulfonyl)butanoic acid

Product 1

HCID 86668754(+/-)-4-(4-Bromophenyl)-N-hydroxy-2-methyl-2-(methylsulfonyl)butanamideYield 96.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (4.50 mL, 50 mmol) was added to a solution of 4-(4-bromophenyl)-2-methyl-2-(methylsulfonyl)butanoic acid (II) (14.69 g, 43.82 mmol) in DCM (300 mL) under nitrogen at ambient temperature, followed by DMF (340 ul). The reaction was stirred until effervescence ceased and then was allowed to stir for 1 hour. O-TMS-hydroxylamine (16.0 mL, 130 mmol) was added via syringe and the suspension was stirred for 1 hour. The reaction was quenched with methanol (60 mL), stirred for 1 hour and concentrated in vacuo to afford a yellow-white solid. The solid was triturated in DCM (200 mL) overnight. The solid was collected by filtration, washed with 1:1 DCM:heptane (2×100 mL), and dried under vacuum to afford the title compound as a white solid (14.85 g, 96.76%). LC-MS m/z 350.0 (M+1). 1H NMR (500 MHz, METHANOL-d4) δ ppm 1.64 (s, 3H) 2.00-2.10 (m, 1H) 2.44-2.58 (m, 2H) 2.61-2.77 (m, 1H) 3.04 (s, 3H) 7.18 (d, J=8.29 Hz, 2H) 7.44 (d, J=8.29 Hz, 2H).

Workup

  1. stirringto stir for 1 hour
  2. stirringthe suspension was stirred for 1 hour
  3. customThe reaction was quenched with methanol (60 mL)
  4. stirringstirred for 1 hour
  5. concentrationconcentrated in vacuo
  6. customto afford a yellow-white solid
  7. customThe solid was triturated in DCM (200 mL) overnight
  8. filtrationThe solid was collected by filtration
  9. washwashed with 1:1 DCM
  10. dry with materialheptane (2×100 mL), and dried under vacuum

Sources & evidence

ORD record
ord-5b0f439f0142477fa938537991240793
Source dataset
uspto-grants-2014_10
Patent number
US08853258B2

Reaction notes

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