Acetic Acid → tert-butyl (3R,4R)-4-(benzylamino)-3-hydroxypiperidine-1-carboxylate

HRID 1670629ノート

反応式

HRID 1670629 の反応式
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][C@@H:19]([NH2:22])[C@H:18]([OH:23])[CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C(O)(=O)C.C([BH3-])#N.[Na+]>C(O)C>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][C@@H:19]([NH:22][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C@H:18]([OH:23])[CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 10727458rac-tert-butyl (3R,4R)-4-amino-3-hydroxypiperidine-1-carboxylate

生成物 1

HCID 67335553tert-butyl (3R,4R)-4-(benzylamino)-3-hydroxypiperidine-1-carboxylate収率 48.5%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒

実験手順

Add benzaldehyde (0.24 mol, 26.3 g) to a solution of racemic trans-4-amino-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.24 mol, 53.7 g), and acetic acid (92 mL) in ethanol (400 mL) and stir the reaction mixture at room temperature for 30 min. Add sodium cyanoborohydride (0.49 mol, 31.2 g) and stir the reaction mixture for 3 h. Quench the reaction mixture with sodium bicarbonate solution and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate. Dissolve the residue in a minimum amount of dichloromethane and add 0.1 N aqueous hydrochloric acid to maintain the pH between 4-5. Discard the organic layer. Wash the acidic aqueous layer three times with dichloromethane and discard the organic layer. Adjust the pH of the aqueous layer between 10-12 and extract with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate to obtain the title compound (35.7 g, 46%) as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 1.35-1.40 (m, 2H), 1.45 (s, 9H), 2.05 (br s 1H), 2.43 (t, 1H), 2.57 (t, 1H), 2.69 (br s, 1H), 3.27 (br s, 1H), 3.70 (d, 1H), 3.94 (d, 1H), 4.15 (br s, 1H), 4.26 (d, 1H), 7.23-7.29 (m, 1H), 7.30-7.32 (m, 2H), 7.33-7.36 (m, 2H).

後処理

  1. customQuench the reaction mixture with sodium bicarbonate solution
  2. extractionextract with dichloromethane
  3. dry with materialDry the organic layer over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. dissolutionDissolve the residue in a minimum amount of dichloromethane
  7. additionadd 0.1 N aqueous hydrochloric acid
  8. temperatureto maintain the pH between 4-5
  9. washWash the acidic aqueous layer three times with dichloromethane
  10. extractionextract with dichloromethane
  11. dry with materialDry the organic layer over anhydrous sodium sulfate
  12. filtrationfilter
  13. concentrationconcentrate

出典と根拠

ORDレコード
ord-8fcf7531a404459380c860404a56fe79
出典データセット
uspto-grants-2011_08
特許番号
US07994164B2

反応ノート

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