Benzyl 4-Hydroxybenzoate → 4-({1-[(Tert-butoxy)carbonyl]pyrrolidin-3-yl}oxy)benzoic acid

HRID 555387ノート

反応式

HRID 555387 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([OH:13])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O:40][C:41](=[O:49])[C:42]1[CH:47]=[CH:46][C:45](O)=[CH:44][CH:43]=1)C1C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([O:13][C:45]2[CH:46]=[CH:47][C:42]([C:41]([OH:49])=[O:40])=[CH:43][CH:44]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 7180Benzyl 4-HydroxybenzoateHCID 11776TriphenylphosphineHCID 44169391-Boc-3-pyrrolidinolHCID 5462977Diethyl azodicarboxylate

生成物 1

HCID 227098074-({1-[(Tert-butoxy)carbonyl]pyrrolidin-3-yl}oxy)benzoic acid収率 69.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a stirred solution of 3-hydroxy-pyrrolidine-1-carboxylic acid t-butyl ester (3 g, 16.02 mmol) in dry THF (75 mL) was added triphenyl phosphine (4.62 g, 17.62 mmol) and 4-hydroxy-benzoic acid benzyl ester (4.02 g, 17.62 mmol). The reaction mixture was cooled to 0° C. and DEAD (2.78 mL, 17.62 mmol) was added dropwise over a period of 30 min. The reaction was gradually brought to room temperature and stirring continued for 16 hrs. The solvent was removed under vacuum and the residue purified by column chromatography (Flash 40) using a gradient of starting from EtOAc-heptane 1:20 to 1:5. Desired fractions were collected and the solvent evaporated in vacuo. The residue was dissolved in EtOH (80 mL) and 10% Pd/C (0.5 g) was added and the mixture was hydrogenated for 16 hrs. The mixture was filtered and the volatiles were evaporated in vacuo affording 3.4 g (69%) of 3-(4-carboxy-phenoxy)-pyrrolidine-1-carboxylic acid t-butyl ester as a solid.

後処理

  1. customwas gradually brought to room temperature
  2. customThe solvent was removed under vacuum
  3. customthe residue purified by column chromatography (Flash 40)
  4. customDesired fractions were collected
  5. customthe solvent evaporated in vacuo
  6. dissolutionThe residue was dissolved in EtOH (80 mL)
  7. addition10% Pd/C (0.5 g) was added
  8. waitthe mixture was hydrogenated for 16 hrs
  9. filtrationThe mixture was filtered
  10. customthe volatiles were evaporated in vacuo

出典と根拠

ORDレコード
ord-dee2548d347f4a3abf9490eb41fb0846
出典データセット
uspto-grants-2011_11
特許番号
US08053447B2

反応ノート

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