Hydrochloric Acid → 1-(4-Methoxy-benzoyl)-pyrrolidine-3,3-dicarboxylic acid ethyl ester

HRID 2060237ノート

反応式

HRID 2060237 の反応式
[CH2:1]([O:3][C:4]([C:6]1([C:21]([O:23]CC)=[O:22])[CH2:10][CH2:9][N:8]([C:11](=[O:20])[C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[CH2:7]1)=[O:5])[CH3:2].O.C(OCC)(=O)C.Cl>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1([C:21]([OH:23])=[O:22])[CH2:10][CH2:9][N:8]([C:11](=[O:20])[C:12]2[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=2)[CH2:7]1)=[O:5])[CH3:2]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 8857Ethyl AcetateHCID 593222271-(4-Methoxy-benzoyl)-pyrrolidine-3,3-dicarboxylic acid diethyl ester

生成物 1

HCID 593222241-(4-Methoxy-benzoyl)-pyrrolidine-3,3-dicarboxylic acid ethyl ester収率 53.4%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
30 °C

実験手順

1-(4-Methoxy-benzoyl)-pyrrolidine-3,3-dicarboxylic acid diethyl ester (679.9 g, 1.95 mol) (see Preparation 7) in acetonitrile (1000 mL) was added to pH 7 buffer solution (10 L, 0.1M potassium phosphate) then Savinase 16T Type W enzyme (3200 g) was added and the resulting slurry was heated to 30° C. The pH of the reaction mixture was kept at 8.5 using a pH stat (TIM856 Titration Manager) and stirred for 6 days. Water (6 L) and ethyl acetate (12 L) was added to the reaction mixture then acidified to pH1 using 2M HCl aqueous solution (6 L). This was filtered through Arbocel™ and the organic layer was separated, washed with water (5 L) then extracted with 0.5M NaOH aqueous solution (7 L). The aqueous phase was acidified using 2M HCl aqueous solution (5 L) and extracted with ethyl acetate (6.5 L). The organic phase was concentrated under reduced pressure to afford the title compound as an orange oil (334.3 g, 53%). (92.9:7.1 ratio of isomers)

後処理

  1. filtrationThis was filtered through Arbocel™
  2. customthe organic layer was separated
  3. washwashed with water (5 L)
  4. extractionthen extracted with 0.5M NaOH aqueous solution (7 L)
  5. extractionextracted with ethyl acetate (6.5 L)
  6. concentrationThe organic phase was concentrated under reduced pressure

出典と根拠

ORDレコード
ord-96a25d6072234f0bbeea1697053899f0
出典データセット
uspto-grants-2012_10
特許番号
US08278343B2

反応ノート

読み込み中…