Ethyl Acetate → 4-{1-[2,5-Difluoro-4-(1-hydroxy-ethyl)-phenyl]-piperidin-4-ylideneaminooxy}-piperidine-1-carboxylic acid isopropyl ester

HRID 2066861ノート

反応式

HRID 2066861 の反応式
[BH4-].[Na+].[CH:3]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([O:15][N:16]=[C:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:28]=[C:27]([F:29])[C:26]([C:30](=[O:32])[CH3:31])=[CH:25][C:24]=3[F:33])[CH2:19][CH2:18]2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])[CH3:4].C(OCC)(=O)C>CO.C([O-])(O)=O.[Na+]>[CH:3]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([O:15][N:16]=[C:17]2[CH2:18][CH2:19][N:20]([C:23]3[CH:28]=[C:27]([F:29])[C:26]([CH:30]([OH:32])[CH3:31])=[CH:25][C:24]=3[F:33])[CH2:21][CH2:22]2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])[CH3:4]

参加物

6

反応物 3

HCID 8857Ethyl AcetateHCID 4311764Sodium borohydrideHCID 866550104-[1-(4-Acetyl-2,5-difluoro-phenyl)-piperidin-4-ylideneaminooxy]-piperidine-1-carboxylic acid isopropyl ester

生成物 1

HCID 583335224-{1-[2,5-Difluoro-4-(1-hydroxy-ethyl)-phenyl]-piperidin-4-ylideneaminooxy}-piperidine-1-carboxylic acid isopropyl ester

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

NaBH4 (0.15 g, 3.9 mmol) was added at 0° C. to a stirred solution of 50a (0.15 g, 0.34 mmol) in 5 mL of methanol. After 1 h, the mixture was diluted with 10 mL of saturated NaHCO3 and stirred for 20 minutes. The mixture was poured into ethyl acetate (25 mL), washed twice with brine (25 mL), dried and concentrated under vacuum. The residue was purified on an AS-H column (elution with 5% EtOH+0.1% triethylamine in hexane) to afford the 2 enantiomers of 4-{1-[2,5-difluoro-4-(1-hydroxy-ethyl)-phenyl]-piperidin-4-ylideneaminooxy}-piperidine-1-carboxylic acid isopropyl ester 50-1, LC-MS 422.2 (MFE-18), tR=6.45 (Method 2). EC50: 48 nM. 78 mg of the first enantiomer and 46 mg of the second enantiomer were obtained.

後処理

  1. washwashed twice with brine (25 mL)
  2. customdried
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified on an AS-H column (elution with 5% EtOH+0.1% triethylamine in hexane)

出典と根拠

ORDレコード
ord-37e9fc74101c4b4899f526f39dd16d0c
出典データセット
uspto-grants-2012_10
特許番号
US08293729B2

反応ノート

読み込み中…