Boron trifluoride etherate → HCID 58550804、化合物

HRID 1908045ノート

反応式

HRID 1908045 の反応式
[CH:1]([O:8][CH2:9][CH3:10])([O:5][CH2:6][CH3:7])OCC.B(F)(F)F.CCOCC.[F:20][C:21]1[CH:22]=[C:23]2[C:40](=[CH:41][CH:42]=1)[O:39][C:26]1([CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]1)[CH2:25][C:24]2=[O:43].CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:9]([O:8][CH:1]([O:5][CH2:6][CH3:7])[CH:25]1[C:26]2([CH2:27][CH2:28][N:29]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[CH2:30][CH2:31]2)[O:39][C:40]2[C:23](=[CH:22][C:21]([F:20])=[CH:42][CH:41]=2)[C:24]1=[O:43])[CH3:10]

参加物

7

反応物 5

HCID 8000Boron trifluoride etherateHCID 31214Ethyl orthoformateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 11759463Tert-butyl 6-fluoro-4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate

生成物 1

HCID 58550804HCID 58550804、化合物収率 22%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒3 回

反応条件

温度
0 °C

実験手順

To triethyl orthoformate (20.2 mL, 121.5 mmol) in dry dichloromethane (115 mL) under argon at −10° C. was added drop-wise BF3.OEt2 (15.4 mL, 121.5 mmol). The solution was allowed to warm to 0° C. and was stirred for 10 minutes. After, the solution was cooled to −78° C. prior to the slow drop-wise addition of tert-butyl 6-fluoro-4-oxo-spiro[chromane-2,4′-piperidine]-1′-carboxylate (13.6 g, 40.5 mmol) in dichloromethane (10 mL). iPr2NEt (24.7 mL, 141.7 mmol) was added drop-wise over 30 minutes, and the mixture was slowly warmed to room temperature and was stirred at 25° C. for 2 hours. The reaction mixture was diluted with the addition of dichloromethane (200 mL) followed by saturated aqueous sodium bicarbonate solution (200 mL). The mixture was shaken in a separatory funnel and separated. The organic layer was washed with additional sodium bicarbonate solution (200 mL) and brine (200 mL). The organic layer was dried over sodium sulfate, filtered and concentrated to yield a residue that was purified by silica gel column chromatography (0-25% EtOAc/hexanes gradient) to give tert-butyl 3-(diethoxymethyl)-6-fluoro-4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (3.9 g, 22%). ESI-MS m/z calc. 437.2. found 438.7 (M+1)+. Retention time 2.14 minutes (3 min run).

後処理

  1. temperatureAfter, the solution was cooled to −78° C.
  2. temperaturethe mixture was slowly warmed to room temperature
  3. stirringwas stirred at 25° C. for 2 hours
  4. stirringThe mixture was shaken in a separatory funnel
  5. customseparated
  6. washThe organic layer was washed with additional sodium bicarbonate solution (200 mL) and brine (200 mL)
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield a residue that
  11. customwas purified by silica gel column chromatography (0-25% EtOAc/hexanes gradient)

出典と根拠

ORDレコード
ord-93a649af4d5a49e697c7d1461486a89b
出典データセット
uspto-grants-2013_12
特許番号
US08598164B2

反応ノート

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