1-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid → 1-Cyclobutyl-4-(piperidine carbonyl)-piperazine di-hydrochloride

HRID 734320ノート

反応式

HRID 734320 の反応式
[ClH:1].Cl.[CH:3]1([N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1.C(=O)([O-])O.[Na+].C([O:22][C:23]([N:25]1[CH2:30][CH2:29][CH:28](C(O)=O)[CH2:27][CH2:26]1)=O)(C)(C)C.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.CCOC(C)=O.C1C=NC2N(O)N=NC=2C=1>[ClH:1].[ClH:1].[CH:3]1([N:7]2[CH2:12][CH2:11][N:10]([C:23]([N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)=[O:22])[CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4]1

参加物

8

反応物 4

HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 451567991-Cyclobutylpiperazine dihydrochloride

生成物 1

HCID 688179621-Cyclobutyl-4-(piperidine carbonyl)-piperazine di-hydrochloride収率 127.1%

試薬・触媒・溶媒 3

HCID 181649HOAt触媒HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

1-Cyclobutyl-piperazine di-hydrochloride (D6)(1.8 g) in DMF (15 ml) was stirred with sodium hydrogen carbonate (1.53 g) for 5 min before being added to a DMF (15 ml) solution of 1-tert-butoxycarbonyl-piperidine-4-carboxylic acid (1.94 g), EDCl (3.2 g) and HOAT (0.05 g). After 4 h the reaction was diluted with EtOAc and washed with saturated sodium hydrogen carbonate solution and brine (3×), before being evaporated. The residue was dissolved in a small volume of EtOAc and treated with TFA (90% TFA/water). After 2 h toluene was added and the reaction evaporated and re-evaporated from toluene. The residue was taken up into EtOAc and treated with 2N HCl in diethyl ether. The precipitate was filtered, washed with diethyl ether and dried under vacuum. Crystallisation from ethanol/diethyl ether afforded the title compound (D7)(1.74 g). LCMS electrospray (+ve) 252(MH+).

後処理

  1. washwashed with saturated sodium hydrogen carbonate solution and brine (3×)
  2. custombefore being evaporated
  3. dissolutionThe residue was dissolved in a small volume of EtOAc
  4. additiontreated with TFA (90% TFA/water)
  5. additionAfter 2 h toluene was added
  6. customthe reaction evaporated
  7. customre-evaporated from toluene
  8. additiontreated with 2N HCl in diethyl ether
  9. filtrationThe precipitate was filtered
  10. washwashed with diethyl ether
  11. customdried under vacuum
  12. customCrystallisation from ethanol/diethyl ether

出典と根拠

ORDレコード
ord-6b71c69e5c224e9989cb10127fd68c14
出典データセット
uspto-grants-2009_09
特許番号
US07592347B2

反応ノート

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