盐酸 → (S)-3-[(R)-1-(3-methoxyphenyl)ethylamino]pyrrolidine dihydrochloride

HRID 409596笔记

反应方程式

HRID 409596 反应方程式
[Ca].C([N:9]1[CH2:13][CH2:12][C@H:11]([NH:14][C@@H:15]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=2)[CH3:16])[CH2:10]1)C1C=CC=CC=1.[ClH:25]>CO.O1CCOCC1.[OH-].[Pd+2].[OH-]>[ClH:25].[ClH:25].[CH3:24][O:23][C:19]1[CH:18]=[C:17]([C@H:15]([NH:14][C@H:11]2[CH2:12][CH2:13][NH:9][CH2:10]2)[CH3:16])[CH:22]=[CH:21][CH:20]=1

参与物

7

反应物 3

HCID 313盐酸HCID 5460341钙HCID 58973545(S)-(1-benzylpyrrolidin-3-yl)-[(R)-1-(3-methoxyphenyl)ethyl]amine

产物 1

HCID 67408353(S)-3-[(R)-1-(3-methoxyphenyl)ethylamino]pyrrolidine dihydrochloride

试剂、催化剂与溶剂 3

HCID 9942167氢氧化钯催化剂HCID 887(5BETA,17BETA)-17-羟基-17-(甲基-D3)-2'H-雄甾-2-烯并[3,2-C]吡唑-5'(1'H)-酮溶剂HCID 312751,4-二氧六环溶剂

实验过程

To a solution of 8.0 g of (R)-1-benzyl-3-pyrrolidinol and 16.5 ml of diisopropylethylamine dissolved in 400 ml of methylene chloride was added dropwise a solution of 13.4 g of anhydrous trifluoromethanesulfonic acid in 50 ml of a methylene chloride at −20° C. or lower. The reaction mixture was stirred for 15 minutes while maintaining it to −20° C., then, a solution of 9.88 g of (R)-1-(3-methoxyphenyl)ethylamine in 100 ml of methylene chloride was added dropwise to the mixture at −20° C. or lower, and the reaction mixture was stirred at room temperature for 16 hours. To the reaction mixture were added a saturated aqueous sodium bicarbonate solution and chloroform, the mixture was stirred and the liquids were separated. The organic layer was dried and concentrated, and the residue was purified by silica gel column chromatography (chloroform:methanol=1:0→50:1) and NH silica gel column chromatography (hexane:ethyl acetate=25:1→10:1) to obtain 3.98 g of (S)-(1-benzylpyrrolidin-3-yl)-[(R)-1-(3-methoxyphenyl)ethyl]amine. MS•APCI (m/z): 311 [M+H]+ (2) To a solution of 3.67 g of (S)-(1-benzylpyrrolidin-3-yl)-[(R)-1-(3-methoxyphenyl)ethyl]amine dissolved in 100 ml of methanol were added 830 mg of palladium hydroxide and 8.85 ml of a solution of 4M hydrochloric acid in dioxane, and the mixture was shaked under hydrogen atmosphere at 3 atm at room temperature for 3 days. Palladium hydroxide was removed, and the solvent was evaporated. To the residue was added methanol, and the resulting precipitates were collected by filtration, washed with methanol and dried to obtain 1.14 g of (S)-3-[(R)-1-(3-methoxyphenyl)-ethylamino]pyrrolidine dihydrochloride (the following Reference example Table, Reference example 1.001).

后处理

  1. customPalladium hydroxide was removed
  2. customthe solvent was evaporated
  3. additionTo the residue was added methanol
  4. customthe resulting precipitates
  5. filtrationwere collected by filtration
  6. washwashed with methanol
  7. customdried

来源与证据

ORD记录
ord-d42f3c1bd92d4c1fa829753927f3d5ee
来源数据集
uspto-grants-2014_06
专利号
US08759387B2

反应笔记

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