Methyl vinyl ketone → N-benzyl-2-nitro-N-(3-oxobutyl)benzenesulfonamide

HRID 526721Notes

Reaction equation

HRID 526721 reaction equation
[CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[N+:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[S:25](Cl)(=[O:27])=[O:26])([O-:18])=[O:17].[CH:29]([C:31]([CH3:33])=[O:32])=[CH2:30]>ClCCl.CCCCCCC.CC(C)([O-])C.[K+]>[CH2:1]([N:8]([CH2:30][CH2:29][C:31](=[O:32])[CH3:33])[S:25]([C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[N+:16]([O-:18])=[O:17])(=[O:27])=[O:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 6570Methyl vinyl ketoneHCID 7504BenzylamineHCID 8471TriethylamineHCID 155402-Nitrobenzenesulfonyl chloride

Product 1

HCID 71152136N-benzyl-2-nitro-N-(3-oxobutyl)benzenesulfonamideYield 87%

Reagents, catalysts & solvents 3

HCID 23665647Potassium tert-butoxideCatalystHCID 6344DichloromethaneSolvent2×HCID 8900HeptaneSolvent

Conditions

Temperature
2.5 °C

Procedure

To a solution of benzylamine (10.92 ml, 100 mmol) in dichloromethane (DCM) (150 ml) was added triethylamine (13.67 ml, 100 mmol) followed by a solution of 2-nitrobenzene-1-sulfonyl chloride (22.16 g, 100 mmol) in DCM (70 ml) at 5-10° C. with stirring. The mixture was stirred for 1 hour (complete by HPLC), stirring continued for 1 hour, washed with water, brine, most of DCM removed on a rotavap, Ethyl acetate (150 ml) was added, another 25-30 ml distilled off under reduced pressure. To the resulting solution potassium tert-butoxide (0.561 g, 5.00 mmol) was added followed by methyl vinyl ketone (9.07 ml, 110 mmol) with stirring in one portion at 20-25° C. The mixture was stirred for 1 hour at 20-25° C., diluted with heptane (70 ml), washed with brine+1N HCl (5 ml), organic phase was dried (MgSO4), evaporated to approx 100 ml, seeded with crystals of compound F (crystallisation started), cooled to 0-5° C., diluted slowly with heptane to approx 200 ml. The mixture was aged in ice for 1 hour, crystals collected, washed with heptane, dried on air to give N-benzyl-2-nitro-N-(3-oxobutyl)benzenesulfonamide (31.4 g, 87 mmol, 87% yield).

Workup

  1. stirringThe mixture was stirred for 1 hour (complete by HPLC)
  2. stirringstirring
  3. washwashed with water, brine, most of DCM
  4. customremoved on a rotavap
  5. additionEthyl acetate (150 ml) was added
  6. distillationanother 25-30 ml distilled off under reduced pressure
  7. stirringwith stirring in one portion at 20-25° C
  8. stirringThe mixture was stirred for 1 hour at 20-25° C.
  9. washwashed with brine+1N HCl (5 ml), organic phase
  10. dry with materialwas dried (MgSO4)
  11. customevaporated to approx 100 ml
  12. additiondiluted slowly with heptane to approx 200 ml
  13. waitThe mixture was aged in ice for 1 hour
  14. customcrystals collected
  15. washwashed with heptane
  16. customdried on air

Sources & evidence

ORD record
ord-bd5de7bf08f64e5194e673f6f6eed4a3
Source dataset
uspto-grants-2016_05
Patent number
US09346751B2

Reaction notes

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