Hydrochloric Acid → 9-Methyl(aminosulfonyl)fluorene-9-carboxylic acid ethyl ester

HRID 1073323Notes

Reaction equation

HRID 1073323 reaction equation
[CH2:1]([O:3][C:4]([CH:6]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[CH:10][CH:11]=2)=[O:5])[CH3:2].C(=O)([O-])[O-].[K+].[K+].BrC[S:27]([NH2:30])(=[O:29])=[O:28].I[CH2:32]S(N)(=O)=O.Cl>CN(C)C=O.O>[CH2:1]([O:3][C:4]([C:6]1([CH3:32])[C:7]2[C:8]([S:27]([NH2:30])(=[O:29])=[O:28])=[CH:9][CH:10]=[CH:11][C:12]=2[C:13]2[C:18]1=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:5])[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 519939IodomethanesulfonamideHCID 596964Ethyl 9H-fluorene-9-carboxylateHCID 12268467Bromomethanesulfonamide

Product 1

HCID 541125249-Methyl(aminosulfonyl)fluorene-9-carboxylic acid ethyl esterYield 31%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of fluorene-9-carboxylic acid ethyl ester (1) (11 g, 46.2 mmoL), potassium carbonate (6.4 g, 46.2 mmoL, 1 eq) and a mixture of bromomethanesulfonamide and iodomethanesulfonamide [prepared from bromomethanesulfonyl chloride see, Trice et al., J. Org. Chem., 32, 990(1967) by reaction with ammonia gas in cold ether followed by reaction with excess sodium iodide in refluxing acetonitrile] (9.1 g, 1 eq) in dry dimethylformamide (100 mL, from sieves) was stirred under nitrogen for 18 h. Water (200 mL) was then added and the solution was acidified with 1N aqueous hydrochloric acid (100 mL) and extracted with ethyl acetate (3×100 mL). The combined organic phases were then washed with brine (3×200 mL), dried (MgSO4), and concentrated. The residue was purified by column chromatography on silica gel using 40% ethyl acetate in hexane to provide 4.8g (31%) of product (2): mp 150°-156° C.; IR (KBr) 3360, 1710, 740, 725 cm-1 ; 1H NMR (CDCl3, 200 MHz) 7.78-7.69 (m, 4 H), 7.50-7.32 (m, 4 H), 4.38 (bs, 2 H, exchangeable), 4.12 (q. 2 H), 4.11 (s, 2 H), 1.12 (t, 3 H), MS m/z 331 (M+), 178 (base peak).

Workup

  1. extractionextracted with ethyl acetate (3×100 mL)
  2. washThe combined organic phases were then washed with brine (3×200 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography on silica gel using 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-4db2bbc8844f4c7a99fb728fcb231261
Source dataset
uspto-grants-1990_11
Patent number
US04968809

Reaction notes

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