Triethylamine → 4-[2-(5-Bromo-4-fluoro-2-methyl-phenyl)-acetylamino]-1-methoxy-piperidine-4-carboxylic acid methyl ester

HRID 1022387ノート

反応式

HRID 1022387 の反応式
[Br:1][C:2]1[C:3]([F:13])=[CH:4][C:5]([CH3:12])=[C:6]([CH2:8][C:9]([OH:11])=O)[CH:7]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.C(N(CC)CC)C.Cl.[CH3:34][O:35][C:36]([C:38]1([NH2:46])[CH2:43][CH2:42][N:41]([O:44][CH3:45])[CH2:40][CH2:39]1)=[O:37]>O1CCCC1>[CH3:34][O:35][C:36]([C:38]1([NH:46][C:9](=[O:11])[CH2:8][C:6]2[CH:7]=[C:2]([Br:1])[C:3]([F:13])=[CH:4][C:5]=2[CH3:12])[CH2:43][CH2:42][N:41]([O:44][CH3:45])[CH2:40][CH2:39]1)=[O:37]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 596146012-(5-Bromo-4-fluoro-2-methylphenyl)acetic acidHCID 666317834-Amino-1-methoxy-piperidine-4-carboxylic acid methyl ester hydrochloride

生成物 1

HCID 596145984-[2-(5-Bromo-4-fluoro-2-methyl-phenyl)-acetylamino]-1-methoxy-piperidine-4-carboxylic acid methyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A suspension of (5-bromo-4-fluoro-2-methyl-phenyl)-acetic acid (8.0 g) and 1,1′-carbonyldiimidazole (5.8 g) in tetrahydrofuran (150 ml) is heated at reflux for 30 minutes. Upon cooling to room temperature, triethylamine (9.0 ml) and 4-amino-1-methoxy-piperidine-4-carboxylic acid methyl ester hydrochloride salt (13.8 g) are added and warming at reflux is continued for 3 hours. The cold reaction mixture is poured on water/ethyl acetate, the layers separated, the organic phase washed with brine, dried over sodium sulfate and concentrated. The residue is solubilised in ethyl acetate/cyclohexane 3:1 and purified by filtration on alumina. Yield: 6.83 g of 4-[2-(5-bromo-4-fluoro-2-methyl-phenyl)-acetylamino]-1-methoxy-piperidine-4-carboxylic acid methyl ester as a solid, mp: 192-193° C.

後処理

  1. temperatureis heated
  2. temperatureat reflux for 30 minutes
  3. temperaturewarming
  4. temperatureat reflux
  5. customThe cold reaction mixture
  6. additionis poured on water/ethyl acetate
  7. customthe layers separated
  8. washthe organic phase washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. filtrationpurified by filtration on alumina

出典と根拠

ORDレコード
ord-bb345c2b05b749cd8f1c7bb0a16c61d1
出典データセット
uspto-grants-2014_05
特許番号
US08722578B2

反応ノート

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