Benzophenone imine → 4-(6-Amino-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1822012

反応式

HRID 1822012 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17](Cl)[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=[NH:35])(C1C=CC=CC=1)C1C=CC=CC=1.CC(C)([O-])C.[Na+].C([O-])(=O)C.[Na+].Cl.NO>CO.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:35])[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

10

反応物 5

HCID 136809Benzophenone imineHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 21906058Tert-butyl 4-[(6-chloropyridin-2-yl)oxy]piperidine-1-carboxylateHCID 23676156Sodium t-butoxide

生成物 1

HCID 578937944-(6-Amino-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester収率 98%

試薬・触媒・溶媒 4

HCID 634876Binap, (A+-)-触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 887Methanol溶媒HCID 1140Toluene溶媒

実験手順

Combine 4-(6-chloro-pyridin-2-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (preparation 57, 2.256 g, 7.2 mmol), benzophenone imine (1.568 g, 8.6 mmol), BINAP (269 mg, 0.43 mmol), Pd2(dba)3 (132 mg, 0.144 mmol), sodium t-butoxide (969 mg, 10.08 mmol) and toluene (50 mL) and heat at 95° C. for 12 hr. Quench the reaction with saturated NaHCO3 solution, extract with ethyl acetate three times. Combine the organic layers, dry over Na2SO4, filter and concentrate to give a residue. Dissolve the residue in methanol (70 mL), add sodium acetate (1.42 g, 17.3 mmol) and hydroxylamine hydrochloride (900 mg, 13 mmol), stir at room temperature for 30 min. Partition between 1N NaOH and CH2Cl2, extract the aqueous layer twice with CH2Cl2. Combine the organic layers and wash with saturated NaCl solution, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel, eluting with 12-25% ethyl acetate in hexanes) provides 2.06 g (98%) of the title compound as a yellow solid: mass spectrum (ion spray): 294.1 (M+1); 1H NMR (CDCl3, ppm): 7.35 (t, 1H), 6.08 (d, 1H), 6.06 (d, 1H), 5.09 (m, 1H), 4.32 (s, br, 2H), 3.75 (m, 2H), 3.29 (m, 2H), 1.94 (m, 2H), 1.73 (m, 2H), 1.49 (s, 9H).

後処理

  1. customQuench
  2. customthe reaction with saturated NaHCO3 solution
  3. extractionextract with ethyl acetate three times
  4. dry with materialCombine the organic layers, dry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. customto give a residue
  8. customPartition between 1N NaOH and CH2Cl2
  9. extractionextract the aqueous layer twice with CH2Cl2
  10. washwash with saturated NaCl solution
  11. dry with materialdry over Na2SO4
  12. filtrationfilter
  13. concentrationconcentrate
  14. customto give a residue
  15. washChromatography (silica gel, eluting with 12-25% ethyl acetate in hexanes)

出典と根拠

ORDレコード
ord-2a65ac7d00cf4a91ac1fc7a99d079489
出典データセット
uspto-grants-2009_10
特許番号
US07608629B2

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