Trifluoroacetic acid → (2-Trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diazacyclopenta[a]naphthalen-8-yl)methyl 4-methylbenzenesulfonate

HRID 392676

Reaction equation

HRID 392676 reaction equation
Cl.Cl.[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([O:13][CH2:14][C@@H:15]2[O:20][C:19]3[C:21]([NH2:26])=[C:22]([NH2:25])[CH:23]=[CH:24][C:18]=3[O:17][CH2:16]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1.[F:27][C:28]([F:33])([F:32])[C:29](O)=O>C(Cl)Cl>[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([O:13][CH2:14][CH:15]2[O:20][C:19]3[C:18](=[CH:24][CH:23]=[C:22]4[NH:25][C:29]([C:28]([F:33])([F:32])[F:27])=[N:26][C:21]4=3)[O:17][CH2:16]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86586513[(2R)-7,8-diamino-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate dihydrochloride

Product 1

HCID 22341388(2-Trifluoromethyl-7,8-dihydro-3H-6,9-dioxa-1,3-diazacyclopenta[a]naphthalen-8-yl)methyl 4-methylbenzenesulfonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3.1 g (7.3 mmole) of [(2R)-7,8-diamino-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate dihydrochloride in 50 mL of trifluoroacetic acid was refluxed under nitrogen for 6 hours. The mixture was diluted to 400 mL with methylene chloride, washed with 400 mL of water and with 400 mL of saturated aqueous sodium bicarbonate, dried over magnesium sulfate, filtered and concentrated to a crude foam in vacuum. The crude product was column chromatographed on silica gel with 1% methanol in chloroform and the product fractions combined and concentrated in vacuum to give 3.3 g of the (R)-enantiomer of the title compound as a white solid (m.p. 114-116° C.), which retains one equivalent of chloroform.

Workup

  1. washwashed with 400 mL of water and with 400 mL of saturated aqueous sodium bicarbonate
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to a crude foam in vacuum
  5. customchromatographed on silica gel with 1% methanol in chloroform
  6. concentrationconcentrated in vacuum

Sources & evidence

ORD record
ord-4879152fb38b4a70a3235e3da4bb9941
Source dataset
uspto-grants-2004_10
Patent number
US06803368B2

Linked notes

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