Thionyl Chloride → (2R)-2-((2-(tert-butoxycarbonylamino)ethyl)amino)-3-(2-naphthyl)propionic acid methylester

HRID 366167ノート

反応式

HRID 366167 の反応式
[NH2:1][C@H:2]([CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=1)[C:3]([OH:5])=[O:4].S(Cl)(Cl)=O.[C:21]([O:25][C:26](=[O:31])[NH:27][CH2:28][CH:29]=O)([CH3:24])([CH3:23])[CH3:22].[C:32]([BH3-])#N.[Na+]>CO>[CH3:32][O:4][C:3](=[O:5])[C@H:2]([NH:1][CH2:29][CH2:28][NH:27][C:26]([O:25][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:31])[CH2:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:8]=1

参加物

6

反応物 4

HCID 24386Thionyl ChlorideHCID 2733661D-3-(2-Naphthyl)alanineHCID 4247255tert-butyl N-(2-oxoethyl)carbamateHCID 5003444Sodium cyanoborohydride

生成物 1

HCID 10761819(2R)-2-((2-(tert-butoxycarbonylamino)ethyl)amino)-3-(2-naphthyl)propionic acid methylester収率 41.4%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

(2R)-2-Amino-3-(2-naphthyl)propionic acid (5, 0 g, 23 mmol) was added to methanol (150 ml) and thionylchloride (2.0 ml; 23 mmol) was added dropwise and the mixture was stirred overnight and then refluxed for 2.5 h. The solvent was removed in vacuo and the residue was dissolved in a mixture of methanol (95 ml) and acetic acid (5 ml). (2-Oxoethyl)carbamic acid tert-butyl ester (3.4 g, 23 mmol, prepared as in Dueholm et al. Org. Prep. Proced. Int. (1993), 457), sodium cyanoborohydride (1.9 g, 31 mmol) and molecular sieves (50 g, Fluka, 3 Å) were added and the mixture was left overnight. The mixture was filtered and the filtrate was added to water (200 ml) and extracted with methylene chloride (3×100 ml). The combined organic phases were dried (magnesium sulphate), and the solvent was removed in vacuo. The residue was chromatographed on silica (3×30 cm) to afford 3.55 g of (2R)-2-((2-(tert-butoxycarbonylamino)ethyl)amino)-3-(2-naphthyl)propionic acid methylester.

後処理

  1. additionwas added dropwise
  2. temperaturerefluxed for 2.5 h
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in a mixture of methanol (95 ml) and acetic acid (5 ml)
  5. waitthe mixture was left overnight
  6. filtrationThe mixture was filtered
  7. additionthe filtrate was added to water (200 ml)
  8. extractionextracted with methylene chloride (3×100 ml)
  9. dry with materialThe combined organic phases were dried (magnesium sulphate)
  10. customthe solvent was removed in vacuo
  11. customThe residue was chromatographed on silica (3×30 cm)

出典と根拠

ORDレコード
ord-bc5c56f247f748beb74f1375b02aac3a
出典データセット
uspto-grants-2000_10
特許番号
US06127354

反応ノート

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