Citric Acid → (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride

HRID 1396857ノート

反応式

HRID 1396857 の反応式
[F:1]C1N=C(F)N=C(F)N=1.N1C=CC=CC=1.[CH:16]1([CH2:21][C@H:22]([CH2:26][N:27]([CH:36]=[O:37])[O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:23](O)=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl>[CH:16]1([CH2:21][C@H:22]([CH2:26][N:27]([CH:36]=[O:37])[O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:23]([F:1])=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17]1

参加物

6

反応物 4

HCID 311Citric AcidHCID 1049PyridineHCID 12664Cyanuric fluorideHCID 21305218(R)-3-(Benzyloxy-formyl-amino)-2-cyclopentylmethyl-propionic acid

生成物 1

HCID 86706340(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride収率 64.7%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

2,4,6-Trifluoro-1,3,5-triazine (10.7 g, 79 mmol) was added into a solution of pyridine (6.4 ml, 79 mmol) and (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (WO 2009061879) (22 g, 72.0 mmol) in dichloromethane (348 ml) at room temperature. The resulting solution was stirred overnight. Dichloromethane (300 mL) was added to the reaction solution, followed by 1000 mL of 5% citric acid, and the mixture was filtrated. The solids were washed with DCM (300 ml). The organic layer of the filtrate was separated and washed with sat. NaHCO3 (2×300 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield a yellow oil, which was purified by silica gel chromatography (CombiFlash, Column: 220 g; 0-20% ethyl acetate in hexane; 50 min) to provide (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride (14.32 g, 64.7% yield) as a colorless oil.

後処理

  1. filtrationthe mixture was filtrated
  2. washThe solids were washed with DCM (300 ml)
  3. customThe organic layer of the filtrate was separated
  4. washwashed with sat. NaHCO3 (2×300 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a yellow oil, which
  9. customwas purified by silica gel chromatography (CombiFlash, Column: 220 g; 0-20% ethyl acetate in hexane; 50 min)

出典と根拠

ORDレコード
ord-529b8d9667ae46d48ef4dfaf22d3cf69
出典データセット
uspto-grants-2014_12
特許番号
US08901119B2

反応ノート

読み込み中…