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

HRID 77023ノート

反応式

HRID 77023 の反応式
C1CCC(N=C=NC2CCCCC2)CC1.Cl.[F:17][C:18]1[CH:19]=[C:20]([CH:24]([NH:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:25]([OH:27])=[O:26])[CH:21]=[CH:22][CH:23]=1.C1C=CC2N(O)N=NC=2C=1.[N:45]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[C@@H:47](O)[CH2:46]2>C1COCC1>[N:45]12[CH2:52][CH2:51][CH:48]([CH2:49][CH2:50]1)[C@@H:47]([O:26][C:25](=[O:27])[CH:24]([C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([F:17])[CH:19]=1)[NH:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:46]2

参加物

6

反応物 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 914043-Quinuclidinol, (-)-HCID 67124831HCID 67124831、化合物

生成物 1

HCID 58556978(R)-quinuclidin-3-yl 2-(3-fluorophenyl)-2-(phenylamino)acetate収率 56%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

PS-DCC (982 mg, 1.31 mmol, loading: 1.33 mmol/g) is suspended in dry THF (15 mL). (3-fluoro-phenyl)-phenylamino-acetic acid hydrochloride (I98) (184 mg, 0.65 mmol), HOBT (200 mg, 1.31 mmol), and (R)-quinuclidin-3-ol (249 mg, 1.96 mmol) are added and the mixture is shaken at RT overnight. PS-DCC is filtered off and the filtrate is evaporated. The residue is dissolved in EtOAc and washed with NaHCO3, water and brine. The organic layer is dried over Na2SO4, filtered and evaporated to dryness. The crude compound is purified by filtration through a pad of silica-gel using DCM/MeOH=9/1 as the eluent. The title compound is obtained as a colorless oil (129 mg, 56% yield, mixture of diastereoisomers).

後処理

  1. filtrationPS-DCC is filtered off
  2. customthe filtrate is evaporated
  3. dissolutionThe residue is dissolved in EtOAc
  4. washwashed with NaHCO3, water and brine
  5. dry with materialThe organic layer is dried over Na2SO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. filtrationThe crude compound is purified by filtration through a pad of silica-gel

出典と根拠

ORDレコード
ord-25258dfd8af94a2a812df00fbbfd2592
出典データセット
uspto-grants-2014_09
特許番号
US08835682B2

反応ノート

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