Morpholine → (5-Bromo-4-methylthiophen-2-yl)(morpholin-4-yl)methanone

HRID 606590ノート

反応式

HRID 606590 の反応式
CO[C:3]([C:5]1[S:6][C:7]([Br:11])=[C:8]([CH3:10])[CH:9]=1)=[O:4].[OH-].[Na+].BrC1SC(C(O)=O)=CC=1C.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>CCO.O.CN(C=O)C.CCOC(C)=O>[Br:11][C:7]1[S:6][C:5]([C:3]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[O:4])=[CH:9][C:8]=1[CH3:10]

参加物

11

反応物 6

HCID 8083MorpholineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2795489Methyl 5-bromo-4-methylthiophene-2-carboxylateHCID 218994595-Bromo-4-methylthiophene-2-carboxylic acid

生成物 1

HCID 67047076(5-Bromo-4-methylthiophen-2-yl)(morpholin-4-yl)methanone

試薬・触媒・溶媒 4

HCID 702Ethanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

5-Bromo-4-methyl-thiophene-2-carboxylic acid methyl ester (8.51 mmol) was dissolved in EtOH (100 ml) and NaOH (42.5 mmol) added, as a 1M solution in water. Reaction was heated to 80° C. for 2 h, after which time all starting material had been consumed. Reaction was then concentrated in vacuo and the residue taken up in DCM and shaken with 1M HCl. The resulting biphasic mixture was then filtered and the filtrant washed with hexane and dried under vacuum. This gave 5-Bromo-4-methyl-thiophene-2-carboxylic acid as off white solid: m/z in MS AP−=219, 221 [M−H]−, 6.79 mmol, 80%. 5-Bromo-4-methyl-thiophene-2-carboxylic acid (6.79 mmol) was taken up in 30 ml DMF and morpholine (7.47 mmol), WSC.HCl (7.47 mmol) and HOBt (7.47 mmol) were added. Reaction was stirred at room temperature for 17 h and then diluted with EtOAc, washed with 1M HCl and brine, dried over Na2SO4 and concentrated in vacuo. Flash chromatography of the residue (silica, 33-50% EtOAc in hexane) gave (5-Bromo-4-methyl-thiophen-2-yl)-morpholin-4-yl-methanone as a pale golden oil: m/z in MS ES+=290, 292 [M+H]+, 4.67 mmol, 69%.

後処理

  1. customReaction
  2. customafter which time all starting material had been consumed
  3. customReaction
  4. concentrationwas then concentrated in vacuo
  5. filtrationThe resulting biphasic mixture was then filtered
  6. washthe filtrant washed with hexane
  7. customdried under vacuum
  8. customReaction
  9. stirringwas stirred at room temperature for 17 h
  10. washwashed with 1M HCl and brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-d96bba80fb7c4d03932edfc7208efdb1
出典データセット
uspto-grants-2011_03
特許番号
US07915300B2

反応ノート

読み込み中…