Lithium hydroxide, monohydrate → (1S,4S)-4-((tert-butoxycarbonyl)amino)-1-isopropylcyclopent-2-enecarboxylic acid

HRID 270539ノート

反応式

HRID 270539 の反応式
[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([CH:18]([CH3:20])[CH3:19])([C:14]([O:16]C)=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[OH-].[Li+]>C1COCC1.CO.O>[C:1]([O:5][C:6]([NH:8][C@H:9]1[CH2:13][C@@:12]([CH:18]([CH3:20])[CH3:19])([C:14]([OH:16])=[O:15])[CH:11]=[CH:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

6

反応物 2

HCID 168937Lithium hydroxide, monohydrateHCID 60122269Methyl(1S,4S)-4-[(tert-Butoxycarbonyl)amino]-1-isopropylcyclopent-2-ene-1-carboxylate

生成物 1

HCID 60122256(1S,4S)-4-((tert-butoxycarbonyl)amino)-1-isopropylcyclopent-2-enecarboxylic acid収率 97.1%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of methyl (1S,4S)-4-[(tert-butoxycarbonyl)amino]-1-isopropylcyclopent-2-ene-1-carboxylate (18.42 g, 65 mmol) in THF (500 mL), methanol (500 mL) and water (100 mL) was added lithium hydroxide monohydrate (5.00 g, 119 mmol). The mixture was heated to reflux overnight. After 18 hours, TLC indicated a very trace amount of starting material. The organic solvents were removed in vacuo and the aqueous layer was extracted with ether (200 mL) to remove the unreacted starting material. The aqueous layer was acidified with concentrated HCl to pH=4 while being cooled in an ice bath. The resulting solution was extracted with methylene chloride three times. The extracts were dried over MgSO4 and concentrated to give a solid (17 g). The solid was dissolved in hot ethyl acetate (22 mL) and hexanes (550 mL) were added to the solution. The solution was slowly cooled down to room temperature before putting into a freezer reading at −22 to −24° C. After two days, the crystals were removed off and the liquid was evaporated in vacuo to give the desired product as a white foamy solid (9.78 g, 56%). MS calculated for C14H23NO4: (M+H)+ 270; found 170.1 (M-Boc+H)+.

後処理

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. customThe organic solvents were removed in vacuo
  4. extractionthe aqueous layer was extracted with ether (200 mL)
  5. customto remove the
  6. temperaturewhile being cooled in an ice bath
  7. extractionThe resulting solution was extracted with methylene chloride three times
  8. dry with materialThe extracts were dried over MgSO4
  9. concentrationconcentrated

出典と根拠

ORDレコード
ord-36c945ce2d8f4054a344ccaba94e0252
出典データセット
uspto-grants-2008_11
特許番号
US07449467B2

反応ノート

読み込み中…