Dicyclohexylcarbodiimide → (R)-quinuclidin-3-yl 2-(3-fluorophenyl)-2-(piperidin-1-yl)acetate

HRID 404670ノート

反応式

HRID 404670 の反応式
Cl.[F:2][C:3]1[CH:4]=[C:5]([CH:9]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:10]([OH:12])=[O:11])[CH:6]=[CH:7][CH:8]=1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[N:44]12[CH2:51][CH2:50][CH:47]([CH2:48][CH2:49]1)[C@@H:46](O)[CH2:45]2>C1COCC1>[F:2][C:3]1[CH:4]=[C:5]([CH:9]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)[C:10]([O:12][C@@H:46]2[CH:47]3[CH2:50][CH2:51][N:44]([CH2:49][CH2:48]3)[CH2:45]2)=[O:11])[CH:6]=[CH:7][CH:8]=1

参加物

6

反応物 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 866889312-(3-Fluorophenyl)-2-(piperidin-1-yl)acetic acid hydrochloride

生成物 1

HCID 86688932(R)-quinuclidin-3-yl 2-(3-fluorophenyl)-2-(piperidin-1-yl)acetate収率 58.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

2-(3-Fluorophenyl)-2-(piperidin-1-yl)acetic acid hydrochloride (225 mg, 0.82 mmol), DCC (339 mg, 1.64 mmol), and HOBT (252 mg, 1.64 mmol) were dissolved in dry THF (9 ml). (R)-quinuclidin-3-ol (314 mg, 2.47 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. THF was evaporated, the residue was taken up with EtOAc and washed with sat. NaHCO3, water and brine. The organic layer was dried over Na2SO4, filtered and evaporated to dryness. The crude was purified by flash chromatography (DCM/MeOH=9/1) to obtain (R)-quinuclidin-3-yl 2-(3-fluorophenyl)-2-(piperidin-1-yl)acetate (166 mg, 58.3 yield).

後処理

  1. customTHF was evaporated
  2. washwashed with sat. NaHCO3, water and brine
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude was purified by flash chromatography (DCM/MeOH=9/1)

出典と根拠

ORDレコード
ord-291ff4a0dc1f4a21be766bae9424807b
出典データセット
uspto-grants-2014_06
特許番号
US08748613B2

反応ノート

読み込み中…