Hydrochloric Acid → (R)-3-[(S)-(3,5-dichlorophenoxy)phenylmethyl]pyrrolidine-1-carboxylic acid t-butyl ester

HRID 1427725ノート

反応式

HRID 1427725 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([C@H:13]([OH:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C=O)C.[H-].[Na+].[Cl:28][C:29]1[CH:30]=[C:31](F)[CH:32]=[C:33]([Cl:35])[CH:34]=1.Cl>CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([C@H:13]([O:20][C:31]2[CH:30]=[C:29]([Cl:28])[CH:34]=[C:33]([Cl:35])[CH:32]=2)[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 1370021,3-Dichloro-5-fluorobenzeneHCID 58507559(r)-3-((s)-Hydroxyphenylmethyl)pyrrolidine-1-carboxylic acid t-butyl ester

生成物 1

HCID 66924546(R)-3-[(S)-(3,5-dichlorophenoxy)phenylmethyl]pyrrolidine-1-carboxylic acid t-butyl ester

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

(R)-3-((S)-hydroxyphenylmethyl)pyrrolidine-1-carboxylic acid t-butyl ester (10.0 g, 36.0 mmol) was dissolved in anhydrous DMF (65 mL, 840 mmol). Washed and dried sodium hydride (1.0 g, 43 mmol) was added, and the mixture stirred at room temperature for 15 minutes. 3,5-Dichlorofluorobenzene (10 mL, 80 mmol) was then added, and the mixture stirred at 70° C. for 3 hours. The mixture was cooled to room temperature. EtOAc (200 mL) and 1M HCl (200 mL) was added, mixed, and the phases separated. The organic layer was washed with 2×200 mL of diluted aqueous NaCl, dried over Na2SO4, and concentrated to dryness to yield 19 g of crude product. The crude product was purified on a 300 g SiG column to yield (R)-3-[(S)-(3,5-dichlorophenoxy)phenylmethyl]pyrrolidine-1-carboxylic acid t-butyl ester as a white sticky foam (14.1 g, 91.67% purity).

後処理

  1. washWashed
  2. stirringthe mixture stirred at 70° C. for 3 hours
  3. temperatureThe mixture was cooled to room temperature
  4. additionmixed
  5. customthe phases separated
  6. washThe organic layer was washed with 2×200 mL of diluted aqueous NaCl
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to dryness
  9. customto yield 19 g of crude product
  10. customThe crude product was purified on a 300 g SiG column

出典と根拠

ORDレコード
ord-0f50199d02f547b58fe9e7dc13784191
出典データセット
uspto-grants-2015_01
特許番号
US08933249B2

反応ノート

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