Benzyl chloroformate → Benzyl (3-fluoropiperidin-4-yl)carbamate

HRID 970379ノート

反応式

HRID 970379 の反応式
C([NH:8][C@H:9]1[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][C@H:10]1[F:22])C1C=CC=CC=1.Cl[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25]>C(O)C.[OH-].[OH-].[Pd+2]>[CH2:27]([O:26][C:24]([NH:8][CH:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH:10]1[F:22])=[O:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

参加物

5

反応物 2

HCID 10387Benzyl chloroformateHCID 11312869cis-4-Benzylamino-1-tert-butoxycarbonyl-3-fluoropiperidine

生成物 1

HCID 21948945Benzyl (3-fluoropiperidin-4-yl)carbamate収率 98%

試薬・触媒・溶媒 2

HCID 9942167Palladium hydroxide触媒HCID 702Ethanol溶媒

実験手順

cis-(+)-4-Benzylamino-1-tert-butoxycarbonyl-3-fluoropiperidine [Enantiomer 1] (15.0 g, 0.049 mole) in ethanol (300 ml) was hydrogenated over 20% palladium hydroxide on carbon (4 g) at 30 psi for 5 h, then filtered through celite and evaporated. The crude amine was dissolved in ethyl acetate (100 mL), saturated sodium hydrogen carbonate solution (100 mL) was added followed by benzyl chloroformate (7.6 mL, 0.53 mole) and the mixture stirred vigorously for 4 h. The organic phase was separated dried and evaporated. The product was dissolved in DCM (75 mL) and stirred with TFA (20 mL) for 4 h then evaporated. The residue was basified with sodium carbonate solution, extracted with 10% methanol in DCM and the extracts dried and evaporated to give a white solid (12.1 g, 98%), [α]D+61.10 (MeOH).

後処理

  1. filtrationfiltered through celite
  2. customevaporated
  3. dissolutionThe crude amine was dissolved in ethyl acetate (100 mL)
  4. additionsaturated sodium hydrogen carbonate solution (100 mL) was added
  5. customThe organic phase was separated
  6. customdried
  7. customevaporated
  8. dissolutionThe product was dissolved in DCM (75 mL)
  9. stirringstirred with TFA (20 mL) for 4 h
  10. customthen evaporated
  11. extractionextracted with 10% methanol in DCM
  12. customthe extracts dried
  13. customevaporated

出典と根拠

ORDレコード
ord-3f93811877c04631998a52e2bd240f88
出典データセット
uspto-grants-2007_12
特許番号
US07312212B2

反応ノート

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