Methanol → HCID 56591282、化合物

HRID 1048205ノート

反応式

HRID 1048205 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:27][CH3:28])[C:22](OCC)=[O:23])[C:11](=[O:29])[C@@H:10]([CH2:30][C:31]([OH:33])=[O:32])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[BH4-].[Li+].CO>CCOCC>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:27][CH3:28])[CH2:22][OH:23])[C:11](=[O:29])[C@@H:10]([CH2:30][C:31]([OH:33])=[O:32])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 887MethanolHCID 4148881Lithium borohydrideHCID 56591304HCID 56591304、化合物

生成物 1

HCID 56591282HCID 56591282、化合物

試薬・触媒・溶媒 1

HCID 3283Diethyl Ether溶媒

実験手順

To a solution of 300 mg (0.61 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-ethoxy-1-oxobutan-2-yl)-2-oxopiperidin-3-yl)acetic acid (Example 3) in 12 mL of Et2O was added lithium tetrahydroborate (39.8 mg, 1.83 mmol) at 0° C. After being stirred for 20 min, methanol (37.0 μl, 914 μmol) was added at 0° C. and the resulting solution was stirred at 25° C. for 2 h. The reaction was quenched (10% citric acid), extracted (2×EtOAc) and washed (1×sat. aq. NaCl solution). The combined organic layers were washed with sat. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification by reversed phase preparatory HPLC (Gemini™ Prep C18 5 μm column, Phenomenex, Torrance, Calif.; eluent: 35 to 75% acetonitrile+0.1% TFA in water+0.1% TFA, gradient elution) provided the title compound as a white foam.

後処理

  1. stirringthe resulting solution was stirred at 25° C. for 2 h
  2. customThe reaction was quenched (10% citric acid)
  3. extractionextracted (2×EtOAc)
  4. washwashed (1×sat. aq. NaCl solution)
  5. washThe combined organic layers were washed with sat. NaCl solution
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customPurification
  10. washby reversed phase preparatory HPLC (Gemini™ Prep C18 5 μm column, Phenomenex, Torrance, Calif.; eluent: 35 to 75% acetonitrile+0.1% TFA in water+0.1% TFA, gradient elution)

出典と根拠

ORDレコード
ord-b317aaaea4194c71aa14ca8951945240
出典データセット
uspto-grants-2013_10
特許番号
US08569341B2

反応ノート

読み込み中…