L-Alaninol → Tert-Butyl 4-[2-[3-fluoro-4-((R)-2-hydroxy-1-methylethyl-carbamoyl)phenoxymethyl]pyridin-5-yl]piperidine-1-carboxylate

HRID 42149

反応式

HRID 42149 の反応式
[C:1]([C:4]1[CH:30]=[CH:29][C:7]([O:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([CH:16]3[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]3)=[CH:12][N:11]=2)=[CH:6][C:5]=1[F:31])(O)=[O:2].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[NH2:55][C@@H:56]([CH3:59])[CH2:57][OH:58].C(=O)([O-])O.[Na+]>O1CCCC1>[F:31][C:5]1[CH:6]=[C:7]([CH:29]=[CH:30][C:4]=1[C:1](=[O:2])[NH:55][C@H:56]([CH3:59])[CH2:57][OH:58])[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:18][CH2:17]2)=[CH:12][N:11]=1

参加物

7

反応物 5

HCID 80307L-AlaninolHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 67083327Tert-Butyl 4-[2-(4-carboxy-3-fluorophenoxymethyl)pyridin-5-yl]piperidine-1-carboxylate

生成物 1

HCID 86654262Tert-Butyl 4-[2-[3-fluoro-4-((R)-2-hydroxy-1-methylethyl-carbamoyl)phenoxymethyl]pyridin-5-yl]piperidine-1-carboxylate収率 87.9%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of tert-butyl 4-[2-(4-carboxy-3-fluorophenoxymethyl)pyridin-5-yl]piperidine-1-carboxylate (Example 10) (21 mg, 0.049 mmol), 1-hydroxybenzotriazole monohydrate (9.3 mg, 0.061 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (12 mg, 0.061 mmol) in dry tetrahydrofuran (0.5 mL) was stirred at room temperature for 1 hour followed by the addition of a solution of (S)-(−)-2-amino-1-propanol (7.6 μL, 0.098 mmol) in dry tetrahydrofuran (0.05 mL). The mixture was stirred at room temperature overnight, to which was added saturated aqueous sodium hydrogen carbonate solution and extracted with chloroform. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/1) to give the title compound as a white crystal (21 mg, yield 86%).

後処理

  1. extractionextracted with chloroform
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (chloroform/methanol=100/1)

出典と根拠

ORDレコード
ord-09601bab574c4bba8afd367d1b7dbbbe
出典データセット
uspto-grants-2013_09
特許番号
US08536176B2

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