(R)-diethyl 1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3,3-dicarboxylate → (R)-1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3-carboxylic acid

HRID 1809540ノート

反応式

HRID 1809540 の反応式
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH2:20][CH2:21][C@H:22]4[N:27]3[CH2:30][C:29](C(OCC)=O)([C:31]([O:33]CC)=[O:32])[CH2:28]3)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2]>CO.[OH-].[Na+]>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[CH2:20][CH2:21][C@H:22]4[N:27]3[CH2:30][CH:29]([C:31]([OH:33])=[O:32])[CH2:28]3)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2]

参加物

4

反応物 1

HCID 67313928(R)-diethyl 1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3,3-dicarboxylate

生成物 1

HCID 58344872(R)-1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3-carboxylic acid収率 33.1%

試薬・触媒・溶媒 2

HCID 14798Sodium Hydroxide触媒HCID 887Methanol溶媒

反応条件

温度
50 °C

実験手順

To a stirred solution of crude (R)-diethyl 1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3,3-dicarboxylate (93 mg, 0.17 mmol) in MeOH (2 mL) was added 6 N NaOH (5 drops). The resulting solution was heated to 50° C. in a closed vial. After 24 h the solution was concentrated, dissolved in water, neutralized with 1N HCl, and heated at 100° C. After 15 h, additional 1N HCl was added, and the mixture was stirred at 105° C. for 24 h. The mixture was diluted with water and extracted with DCM and EA. The organic layers were combined, dried over Na2SO4, and purified by preparative HPLC to provide 25 mg (33%) of (R)-1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3-carboxylic acid 202. LCMS-ESI (m/z) calculated for C25H24N4O4: 444.5; found 445.2 [M+H]+, tR=2.55 min. Compound 203 was made in an analogous fashion.

後処理

  1. concentrationAfter 24 h the solution was concentrated
  2. dissolutiondissolved in water
  3. temperatureheated at 100° C
  4. additionadditional 1N HCl was added
  5. additionThe mixture was diluted with water
  6. extractionextracted with DCM and EA
  7. dry with materialdried over Na2SO4
  8. custompurified by preparative HPLC

出典と根拠

ORDレコード
ord-337487925b9547cfa130973631bbae4e
出典データセット
uspto-grants-2013_01
特許番号
US08362048B2

反応ノート

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