Sodium Bicarbonate → Tert-butyl 8-(2,2-difluoroethyl)-10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

HRID 72888

反応式

HRID 72888 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]1[O:24][C:11]2([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[CH2:10][NH:9][CH2:8]1.C(=O)([O-])O.[Na+].FC(F)(F)S(O[CH2:36][CH:37]([F:39])[F:38])(=O)=O>C(O)C.C(Cl)Cl>[F:38][CH:37]([F:39])[CH2:36][N:9]1[CH2:8][CH:7]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[O:24][C:11]2([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:13][CH2:12]2)[CH2:10]1

参加物

6

反応物 3

HCID 516892Sodium BicarbonateHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 70872717tert-Butyl 2-(pyridin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

生成物 1

HCID 86672472Tert-butyl 8-(2,2-difluoroethyl)-10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
80 °C

実験手順

To tert-butyl 10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (63 mg, 0.19 mmol) in ethanol was added sodium hydrogen carbonate (64 mg, 0.76 mmol) followed by the addition of 2,2-difluoroethyl trifluoromethanesulfonate (49 mg, 0.23 mmol) and reaction mixture was heated at 80° C. for 40 minutes. The reaction mixture was cooled to room temperature and diluted with DCM and the organic layer was washed with 1:1 NaOH:NaHCO3 solution. The organics were separated, dried over Na2SO4, filtered and concentrated in vacuo to give tert-butyl 8-(2,2-difluoroethyl)-10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate as an oil. To the oil was added HCl (237.5 μL of 4 M in dioxane, 0.95 mmol) at room temperature under an atmosphere of nitrogen and the reaction mixture was stirred for 30 minutes. The solvent was removed in vacuo and the residue was triturated with ether to give 8-(2,2-difluoroethyl)-10-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane (45 mg, 79%). ESI-MS m/z calc. 297.3. Found 298.4 (M+1)+; Retention time: 0.35 minutes (3 min run).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washthe organic layer was washed with 1:1 NaOH
  3. customThe organics were separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-c855550fa8304214ac8abef28b86a278
出典データセット
uspto-grants-2014_09
特許番号
US08828996B2

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