Diethyl Ether → 2-(Pyridin-3-ylmethyl)quinuclidin-3-amine

HRID 31082ノート

反応式

HRID 31082 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH:8]2[C:13](=O)[CH:12]3[CH2:15][CH2:16][N:9]2[CH2:10][CH2:11]3)[CH:2]=1.CCOCC.C([O-])=O.[NH4+].C([BH3-])#[N:27].[Na+]>CO.[Cl-].[Cl-].[Zn+2]>[NH2:27][CH:13]1[CH:12]2[CH2:15][CH2:16][N:9]([CH2:10][CH2:11]2)[CH:8]1[CH2:7][C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1

参加物

7

反応物 4

HCID 3283Diethyl EtherHCID 2723923Ammonium formateHCID 5003444Sodium cyanoborohydrideHCID 102200302-(Pyridin-3-ylmethyl)quinuclidin-3-one

生成物 1

HCID 223113782-(Pyridin-3-ylmethyl)quinuclidin-3-amine

試薬・触媒・溶媒 2

HCID 3007855Zincchloride触媒HCID 887Methanol溶媒

実験手順

To a stirred solution of 2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-one (3.00 g, 13.9 mmol) in dry methanol (20 mL), under nitrogen, was added a 1 M solution of ZnCl2 in ether (2.78 mL, 2.78 mmol). After stirring at ambient temperature for 30 min, this mixture was treated with solid ammonium formate (10.4 g, 167 mmol). After stirring another hour at ambient temperature, solid sodium cyanoborohydride (1.75 g, 27.8 mmol) was added in portions. The reaction was then stirred at ambient temperature overnight and terminated by addition of water (˜5 mL). The quenched reaction was partitioned between 5 M NaOH (10 mL) and chloroform (20 mL). The aqueous layer was extracted with chloroform (20 mL), and combined organic layers were dried (Na2SO4), filtered and concentrated. This left 2.97 g of yellow gum. GC/MS analysis indicated that the product was a 90:10 mixture of the cis and trans amines, along with a trace of the corresponding alcohol (98% mass recovery).

後処理

  1. stirringAfter stirring another hour at ambient temperature
  2. stirringThe reaction was then stirred at ambient temperature overnight
  3. customterminated by addition of water (˜5 mL)
  4. customThe quenched reaction
  5. customwas partitioned between 5 M NaOH (10 mL) and chloroform (20 mL)
  6. extractionThe aqueous layer was extracted with chloroform (20 mL)
  7. dry with materialwere dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additiona 90:10 mixture of the cis and trans amines

出典と根拠

ORDレコード
ord-f01ce467991f4809b97078d52abff9af
出典データセット
uspto-grants-2008_09
特許番号
US07425561B2

反応ノート

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