Hydrochloric Acid → Ethyl 4-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-methoxyphenyl)propyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate

HRID 1817187Notes

Reaction equation

HRID 1817187 reaction equation
ClC(OC(C)C)=O.[CH2:8]([O:10][C:11]([C:13]1[CH:14]=[CH:15][C:16]2[S:21][CH:20]([CH2:22][CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C:19](=[O:33])[N:18]([CH2:34][C:35]([OH:37])=O)[C:17]=2[CH:38]=1)=[O:12])[CH3:9].CN1CCOCC1.C[Si](C)(C)[O:48][NH2:49].Cl>O1CCCC1>[OH:48][NH:49][C:35](=[O:37])[CH2:34][N:18]1[C:17]2[CH:38]=[C:13]([C:11]([O:10][CH2:8][CH3:9])=[O:12])[CH:14]=[CH:15][C:16]=2[S:21][CH:20]([CH2:22][CH2:23][CH2:24][C:25]2[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=2)[C:19]1=[O:33]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7917Isopropyl chloroformate2×HCID 79724-MethylmorpholineHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 23157938{6-(Ethoxycarbonyl)-2-[3-(4-methoxyphenyl)propyl]-3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl}acetic acid

Product 1

HCID 23157964Ethyl 4-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-methoxyphenyl)propyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

At −15° C., isopropyl chloroformate (2.84 ml) was added dropwise to a solution of {6-(ethoxycarbonyl)-2-[3-(4-methoxyphenyl)propyl]-3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl}acetic acid (10.64 g) and N-methylmorpholine (3.2 ml) in tetrahydrofuran (200 ml). After the dropwise addition of the whole isopropyl chloroformate, the resulting mixture was stirred for 25 minutes and then O-(trimethylsilyl)hydroxylamine (3.52 ml) was added dropwise thereto. After 3 hours, the reaction mixture was poured into a 0.5N aqueous hydrochloric acid solution and extracted with ethyl acetate. The oil layer was washed with a saturated aqueous sodium chloride solution, dehydrated over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by a silica gel chromatography (hexane/ethyl acetate=⅔ to ⅓). To the resulting yellow oil were added toluene and hexane to effect crystallization. The solid obtained was collected by filtration and concentrated under reduced pressure. Ethyl 4-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-methoxyphenyl)propyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate (8.24 g) was obtained as a yellow solid.

Workup

  1. waitAfter 3 hours
  2. extractionextracted with ethyl acetate
  3. washThe oil layer was washed with a saturated aqueous sodium chloride solution
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by a silica gel chromatography (hexane/ethyl acetate=⅔ to ⅓)
  6. additionTo the resulting yellow oil were added toluene and hexane
  7. customcrystallization
  8. customThe solid obtained
  9. filtrationwas collected by filtration
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1394d82dd22d443d9b24ba599111fbb9
Source dataset
uspto-grants-2009_10
Patent number
US07598240B2

Reaction notes

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