Hydrochloric Acid → (Z)-N-Hydroxy-N-methyl-5-fluoro-2-methyl-1-(4-methylthiobenzylidene)inden-3-ylacetamide

HRID 1420719Notes

Reaction equation

HRID 1420719 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)/[C:7](=[CH:11]\[C:12]1[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=1)/[C:6]([CH3:20])=[C:5]2[CH2:21][C:22]([OH:24])=O.C(Cl)(=O)C(Cl)=O.Cl.[CH3:32][NH:33][OH:34].C(N(CC)CC)C.Cl>C(Cl)Cl.CN(C)C=O.O1CCCC1.O.C(OCC)(=O)C>[OH:34][N:33]([CH3:32])[C:22](=[O:24])[CH2:21][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=2)/[C:7](=[CH:11]\[C:12]2[CH:17]=[CH:16][C:15]([S:18][CH3:19])=[CH:14][CH:13]=2)/[C:6]=1[CH3:20]

Participants

12

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 77906N-methylhydroxylamine hydrochlorideHCID 5352624Sulindac Sulfide

Product 1

HCID 86745519(Z)-N-Hydroxy-N-methyl-5-fluoro-2-methyl-1-(4-methylthiobenzylidene)inden-3-ylacetamide

Reagents, catalysts & solvents 6

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (Z)-5-fluoro-2-methyl-1-(4-methylthiobenzylidene)inden-3-ylacetic acid (U.S. Pat. No. 3,647,858; U.S. Pat. No. 3,654,349; J.O.C. Vol. 42, 1914-1919 (1977) (130 mg, 0.38 mmol) in methylene chloride (3 mL) at room temperature there was added oxalyl chloride (96.5 mg, 0.76 mmol) and one drop of N, N-dimethylformamide (DMF). When gassing had subsided another drop of DMF was added and stirring was continued for 30 minutes. This solution was added, at 0° C., to a mixture of N-methyl hydroxylamine hydrochloride (125 mg, 1.5 mmol) and triethylamine (253 mg, 2.5 mmol) in tetrahydrofuran (THF) (5 mL). After 30 minutes at 0° C., the mixture was diluted with water and ethyl acetate and acidified with 1N aqueous HCl. The crude product from the organic extract was crystallized from a mixture of ethyl acetate and hexane to afford the title product as yellow-orange crystals, mp: slow decomp. from 118° C.

Workup

  1. additionwas added
  2. waitAfter 30 minutes at 0° C.
  3. extractionThe crude product from the organic extract
  4. customwas crystallized from a mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-a5336a5a414b4907afdcdcf9754d1d62
Source dataset
uspto-grants-2000_06
Patent number
US06071934

Reaction notes

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