Iodine → n-(4-Iodo-6-thiomorpholin-4-yl-pyridin-3-yl)-2,2-dimethyl-propionamide

HRID 22643

反応式

HRID 22643 の反応式
[CH3:1][C:2]([CH3:19])([CH3:18])[C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([N:12]2[CH2:17][CH2:16][S:15][CH2:14][CH2:13]2)=[CH:10][CH:11]=1)=[O:4].CN(C)CCN(C)C.CC1(C)CCCC(C)(C)N1.C([Li])CCC.[I:43]I.O.O.O.O.O.S([O-])([O-])(=O)=S.[Na+].[Na+]>O1CCCC1.CCCCCC.COC(C)(C)C>[I:43][C:11]1[CH:10]=[C:9]([N:12]2[CH2:17][CH2:16][S:15][CH2:14][CH2:13]2)[N:8]=[CH:7][C:6]=1[NH:5][C:3](=[O:4])[C:2]([CH3:19])([CH3:18])[CH3:1]

参加物

10

反応物 6

HCID 807IodineHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 130352,2,6,6-TetramethylpiperidineHCID 61475Sodium Thiosulfate PentahydrateHCID 225914472,2-Dimethyl-n-(6-thiomorpholin-4-yl-pyridin-3-yl)-propionamideHCID 178418339Butyllithium

生成物 1

HCID 22591449n-(4-Iodo-6-thiomorpholin-4-yl-pyridin-3-yl)-2,2-dimethyl-propionamide収率 63.4%

試薬・触媒・溶媒 3

HCID 8028Tetrahydrofuran溶媒HCID 8058Hexane溶媒HCID 15413tert-Butyl methyl ether溶媒

反応条件

温度
-15 °C

実験手順

Under argon) a solution of 75 g (268 mmol) 2,2-dimethyl-N-(6-thiomorpholin-4-yl-pyridin-3-yl)-propionamide, 187 g (1.61 mol) N,N,N′,N′-tetramethylethylenediamine and 85 g (604 mmol) 2,2,6,6,-tetramethylpiperidine in 750 ml tetrahydrofuran was cooled to −65° C. in a dry ice bath. Within 30 min, 805 ml (1.29 mol) of a 1.6 N n-butyllithium solution in hexane were added dropwise. The reaction mixture was allowed to warm up to −15° C. and was stirred for 3 h at this temperature. After cooling again to −70° C., 354 g (1.40 mol) iodine (dissolved in 1000 ml tetrahydrofuran) were added dropwise during 2 h and stirring was continued for 1 h. The suspension was warmed to −60° C. and was poured into 1000 ml of 30% sodium thiosulfate pentahydrate solution. Then, 750 ml tert-butyl methyl ether were added and the organic layer was separated. The aqueous layer was extracted three times with 750-ml portions of tert-butyl methyl ether and the combined organic layers were dried (sodium sulfate) and evaporated. Flash chromatography gave 68.9 g (63%) of the title compound as light brown crystals.

後処理

  1. temperatureAfter cooling again to −70° C.
  2. stirringstirring
  3. waitwas continued for 1 h
  4. temperatureThe suspension was warmed to −60° C.
  5. customthe organic layer was separated
  6. extractionThe aqueous layer was extracted three times with 750-ml portions of tert-butyl methyl ether
  7. dry with materialthe combined organic layers were dried (sodium sulfate)
  8. customevaporated

出典と根拠

ORDレコード
ord-cde684b0dfb44ff4867ced69a2c281fc
出典データセット
uspto-grants-2005_02
特許番号
US06849624B2

関連ノート

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