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

HRID 1817188Notes

Reaction equation

HRID 1817188 reaction equation
C[Si](C)(C)[O:3][NH2:4].C(=O)([O-])O.[Na+].[CH2:12]([O:14][C:15]([C:17]1[CH:18]=[CH:19][C:20]2[S:25][C@@H:24]([CH2:26][CH2:27][CH2:28][C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=3)[C:23](=[O:37])[N:22]([CH2:38][C:39](O)=[O:40])[C:21]=2[CH:42]=1)=[O:16])[CH3:13]>C1COCC1.ClC(OCC(C)C)=O.CN1CCOCC1>[OH:3][NH:4][C:39](=[O:40])[CH2:38][N:22]1[C:21]2[CH:42]=[C:17]([C:15]([O:14][CH2:12][CH3:13])=[O:16])[CH:18]=[CH:19][C:20]=2[S:25][CH:24]([CH2:26][CH2:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][CH:30]=2)[C:23]1=[O:37]

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 57880327{(2S)-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 3

HCID 79724-MethylmorpholineSolventHCID 8028TetrahydrofuranSolventHCID 62365Isobutyl chloroformateSolvent

Conditions

Temperature
-15 °C

Procedure

In THF (40 ml) was dissolved {(2S)-6-(ethoxycarbonyl)-2-[3-(4-methoxyphenyl)propyl]-3-oxo-2,3-dihydro-4H-1,4-benzothiazin-4-yl}acetic acid (the compound of Reference Example 11) (2.06 g), and isobutyl chloroformate (0.72 ml) and N-methylmorpholine (0.51 ml) were added thereto at −20° C. and stirred at −10 to −20° C. for 30 minutes. After O-(trimethylsilyl)hydroxylamine (0.87 ml) was added thereto, the resulting mixture was warmed up to room temperature and stirred for 1 hour. The reaction mixture was poured into a saturated aqueous sodium hydrogencabonate solution and extracted with ethyl acetate, and the organic layer was washed with a saturated aqueous ammonium chloride solution and a saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate. The drying agent was removed by filtration and the solvent was distilled off under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate and diisopropyl ether to obtain (−)-ethyl 4-[2-(hydroxyamino)-2-oxoethyl]-2-[3-(4-methoxyphenyl)propyl]-3-oxo-3,4-dihydro-2H-1,4-benzothiazine-6-carboxylate (1.69 g, 99.9% e.e.). The optical purity analysis conditions are as follows. [Column: AD-H(CHIRALCEL, DAICEL Chemical Industries Ltd.); detecting wavelength (UV): 254 nm; flow rate: 1.0 ml/min; mobile phase: n-hexane/isopropyl alcohol/TFA=80/20/0.1]

Workup

  1. additionwere added
  2. temperaturethe resulting mixture was warmed up to room temperature
  3. stirringstirred for 1 hour
  4. extractionextracted with ethyl acetate
  5. washthe organic layer was washed with a saturated aqueous ammonium chloride solution
  6. dry with materiala saturated aqueous sodium chloride solution and then dried over anhydrous sodium sulfate
  7. customThe drying agent was removed by filtration
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe residue was recrystallized from a mixed solvent of ethyl acetate and diisopropyl ether

Sources & evidence

ORD record
ord-59206fac71844089b5c894fdfbd33c97
Source dataset
uspto-grants-2009_10
Patent number
US07598240B2

Reaction notes

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