Triethylamine → (S)-tert-Butyl 4-(4-(methoxycarbonyl)piperidin-1-yl)azepane-1-carboxylate

HRID 714536ノート

反応式

HRID 714536 の反応式
[CH:1]1([C:6]([O:8][CH3:9])=[O:7])[CH2:5][CH:4]=[CH:3][CH2:2]1.O=[O+][O-].[NH2:13][C@H:14]1[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][CH2:15]1.CCN(CC)CC.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CO.ClCCCl.C(O)(=O)C>[CH3:9][O:8][C:6]([CH:1]1[CH2:2][CH2:3][N:13]([C@H:14]2[CH2:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][CH2:15]2)[CH2:4][CH2:5]1)=[O:7]

参加物

9

反応物 5

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 24823OzoneHCID 1514118Methyl cyclopent-3-ene-1-carboxylateHCID 32639843(S)-tert-butyl 4-aminoazepane-1-carboxylate

生成物 1

HCID 89590036(S)-tert-Butyl 4-(4-(methoxycarbonyl)piperidin-1-yl)azepane-1-carboxylate収率 64.6%

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 176Acetic Acid溶媒HCID 21226129Dichloromethane methanol溶媒

反応条件

温度
-78 °C

実験手順

Methyl cyclopent-3-ene-1-carboxylate (4.42 g, 35 mmol) was dissolved in DCM/MeOH (160 mL, 3:1) and cooled to −78° C. Ozone was passed through the solution until a blue colour persisted. Excess ozone was purged from the reaction mixture with dry N2. Dimethylsulfide (10 mL) was added and the reaction mixture was warmed to rt, the solvent was removed in vacuo. The residue was added to a solution of tert-butyl (4S)-4-aminoazepane-1-carboxylate (7.5 g, 35 mmol), STAB (18.57 g, 87.6 mmol), NEt3 (4.26 g, 42.1 mmol) and acetic acid (1.8 mL) in DCE (200 mL). The mixture was stirred for 3 hours at rt and was then poured into aqueous Na2CO3 solution. The mixture was extracted with EtOAc (3×200 mL), the organic phase were washed with water (100 mL) and brine (100 mL), dried over Na2SO4. The solvent was removed in vacuo, and the residue was purified by column chromatography (gradient 0% to 25% EtOAc in Petroleum ether) to give tert-butyl (4S)-4-[4-(methoxycarbonyl)piperidin-1-yl]azepane-1-carboxylate (7.7 g, 64.6% yield) as a yellow oil.

後処理

  1. customExcess ozone was purged from the reaction mixture with dry N2
  2. additionDimethylsulfide (10 mL) was added
  3. temperaturethe reaction mixture was warmed to rt
  4. customthe solvent was removed in vacuo
  5. extractionThe mixture was extracted with EtOAc (3×200 mL)
  6. washthe organic phase were washed with water (100 mL) and brine (100 mL)
  7. dry with materialdried over Na2SO4
  8. customThe solvent was removed in vacuo
  9. customthe residue was purified by column chromatography (gradient 0% to 25% EtOAc in Petroleum ether)

出典と根拠

ORDレコード
ord-e0d84b11a1d64b7b9f28bdf6bffb8a94
出典データセット
uspto-grants-2015_11
特許番号
US09187451B2

反応ノート

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