Potassium Sodium Tartrate → tert-Butyl(3S)-3-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)piperidine-1-carboxylate

HRID 30335

反応式

HRID 30335 の反応式
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]([NH:14][C:15]([NH:17]C(=O)C(Cl)(Cl)Cl)=[O:16])=[C:11]([C:24]([O:26]C)=O)[CH:10]=2)=[CH:5][CH:4]=1.C[Al](C)C.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][CH2:42][C@H:41]([NH2:45])[CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1.CCOC(C)=O.O>[NH2:17][C:15]([NH:14][C:12]1[S:13][C:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)=[CH:10][C:11]=1[C:24]([NH:45][C@H:41]1[CH2:42][CH2:43][CH2:44][N:39]([C:37]([O:36][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:38])[CH2:40]1)=[O:26])=[O:16]

参加物

8

反応物 4

HCID 9357Potassium Sodium TartrateHCID 1501975tert-butyl (3S)-3-aminopiperidine-1-carboxylateHCID 11546916Methyl 5-(4-methoxyphenyl)-2-({[(trichloroacetyl)amino]carbonyl}amino)thiophene-3-carboxylateHCID 16682925Trimethylaluminum

生成物 1

HCID 69271788tert-Butyl(3S)-3-({[2-[(aminocarbonyl)amino]-5-(4-methoxyphenyl)-3-thienyl]carbonyl}amino)piperidine-1-carboxylate収率 67%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of methyl 5-(4-methoxyphenyl)-2-({[(trichloroacetyl)amino]carbonyl}amino)thiophene-3-carboxylate (1.0 g, 2.2 mmol) in dry THF (20 mL) was added a solution of [Me2Al-3-Boc-(S)-3-aminopiperidine] in THF (which was preformed by the addition of Me3Al (2.0 M in hexanes, 2.2 nL, 4.4 mmol) to a solution of (S)-3-Amino-piperidine-1-carboxylic acid tert-butyl ester (0.89 g, 4.4 mmol) in 10 mL THF at −78° C. followed by warming to room temperature for an additional 15 min). The resulting orange-colored solution was stirred overnight at room temperature. The reaction mixture was cooled with ice and a 10% aqueous solution of Rochelle's salt was added slowly to quench the reaction. The resulting biphasic solution was warmed to room temperature and stirred for an additional 1 h. The mixture was diluted with EtOAc and H2O, the aqueous layer was extracted with EtOAc (3×) and the combined organic extracts were washed with H2O, brine and dried (Na2SO4). Evaporation gave a pale orange solid. Purification by column chromatography (SiO2, 50% EtOAc/hexanes) gave 0.70 g (67%) of a light yellow solid. LC/MS (APCI, ES, M+H=475).

後処理

  1. temperatureThe reaction mixture was cooled with ice
  2. customto quench
  3. customthe reaction
  4. temperatureThe resulting biphasic solution was warmed to room temperature
  5. stirringstirred for an additional 1 h
  6. extractionthe aqueous layer was extracted with EtOAc (3×)
  7. washthe combined organic extracts were washed with H2O, brine
  8. dry with materialdried (Na2SO4)
  9. customEvaporation
  10. customgave a pale orange solid
  11. customPurification by column chromatography (SiO2, 50% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-d66aea6f837c4ae596788447543f1d0d
出典データセット
uspto-grants-2008_09
特許番号
US07423061B2

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