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 1360208ノート

反応式

HRID 1360208 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 79724-Methylmorpholine溶媒HCID 8028Tetrahydrofuran溶媒HCID 62365Isobutyl chloroformate溶媒

反応条件

温度
-15 °C

実験手順

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]

後処理

  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

出典と根拠

ORDレコード
ord-fe618246f7664ba7a279f656a6329715
出典データセット
uspto-grants-2011_02
特許番号
US07879843B2

反応ノート

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