Triethylamine → 1-Methyl-4-(pyrrolidin-1-yl-carbonyl)piperidine

HRID 404246

反応式

HRID 404246 の反応式
C(Cl)(=O)C(Cl)=O.Cl.[CH3:8][N:9]1[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]1.[NH:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1.C(N(CC)CC)C.[OH-].[Na+]>C1COCC1.O.CN(C=O)C>[CH3:8][N:9]1[CH2:10][CH2:11][CH:12]([C:15]([N:18]2[CH2:22][CH2:21][CH2:20][CH2:19]2)=[O:17])[CH2:13][CH2:14]1

参加物

9

反応物 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 31268PyrrolidineHCID 65578Oxalyl chlorideHCID 27600434-Piperidinecarboxylic acid, 1-methyl-, hydrochloride (1:1)

生成物 1

HCID 179803551-Methyl-4-(pyrrolidin-1-yl-carbonyl)piperidine収率 100.1%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
5 °C

実験手順

Add oxalyl chloride (5.08 mL, 0.058 mol) dropwise to a suspension of 1-methyl-4-carboxypiperidine HCl (10 g, 0.056 mol) in THF (100 mL) in the presence of a catalytic amount of DMF (0.1 mL) at room temperature. Stir for 1 hr. and then heat the mixture at reflux until gas emission stops (about 1 hr.). Cool the white suspension to 5° C. and add a solution of pyrrolidine (7.92 g, 0.111 mol) and triethylamine (16.9 g, 0.167 mol) dropwise over 30 min at a temperature between 5 and 13° C. Stir the suspension for 30 min. at 10° C. and then warm to room temperature. Quench the reaction mixture by adding 30% NaOH (20 mL, 0.2 mol) and water (10 mL). Decant the aqueous layer and extract with THF (200 mL). Combine the organic layers, dry over Na2CO3, and evaporate under vacuum at 40° C. Solubilize the resulting oil in cyclohexane (200 mL). Evaporate under reduced pressure at 40° C. to give a white solid (11 g). 1-Teat the white solid (11 g) under reflux in cyclohexane (50 mL) until completely dissolved. Cool the solution to room temperature and stir at room temperature for 2 hr. Filter the suspension wash the crystals with cyclohexane (10 mL). Dry the white crystals under reduced pressure at 40° C. to provide the title intermediate (7.76 g, 75% yield).

後処理

  1. temperatureand then heat the mixture
  2. temperatureat reflux until gas emission
  3. custom(about 1 hr.)
  4. stirringStir the suspension for 30 min. at 10° C.
  5. temperaturewarm to room temperature
  6. customQuench the reaction mixture
  7. customDecant the aqueous layer
  8. extractionextract with THF (200 mL)
  9. dry with materialCombine the organic layers, dry over Na2CO3
  10. customevaporate under vacuum at 40° C
  11. customEvaporate under reduced pressure at 40° C.

出典と根拠

ORDレコード
ord-50110102a2694632a4fceb4e5aae1ab3
出典データセット
uspto-grants-2014_06
特許番号
US08748459B2

関連ノート

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