tert-Butanol → tert-Butyl {1-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}carbamate

HRID 876256ノート

反応式

HRID 876256 の反応式
C([N:3]([CH2:6]C)CC)C.P(N=[N+]=[N-])(=O)(OC1C=CC=CC=1)[O:9]C1C=CC=CC=1.[O:27]1[C:31]2([CH2:36][CH2:35][N:34]([C:37]([N:39]3[CH2:44][CH:43]([C:45]4[CH:50]=[CH:49][C:48]([C:51]([F:54])([F:53])[F:52])=[CH:47][CH:46]=4)[CH2:42][CH:41](C(O)=O)[CH2:40]3)=[O:38])[CH2:33][CH2:32]2)[O:30][CH2:29][CH2:28]1.[C:58]([OH:62])([CH3:61])([CH3:60])[CH3:59]>>[O:27]1[C:31]2([CH2:32][CH2:33][N:34]([C:37]([N:39]3[CH2:44][CH:43]([C:45]4[CH:50]=[CH:49][C:48]([C:51]([F:54])([F:53])[F:52])=[CH:47][CH:46]=4)[CH2:42][CH:41]([NH:3][C:6](=[O:9])[O:62][C:58]([CH3:61])([CH3:60])[CH3:59])[CH2:40]3)=[O:38])[CH2:35][CH2:36]2)[O:30][CH2:29][CH2:28]1

参加物

5

反応物 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 667617021-(1,4-Dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-5-[4-(trifluoromethyl)phenyl]piperidine-3-carboxylic acid

生成物 1

HCID 68075238tert-Butyl {1-(1,4-dioxa-8-azaspiro[4.5]dec-8-ylcarbonyl)-5-[4-(trifluoromethyl)phenyl]piperidin-3-yl}carbamate

実験手順

Activated molecular sieves 4 Å (about 8.4 g), 1.74 ml of triethylamine (12.5 mmol) and 3.15 g (11.4 mmol) of diphenyl phosphorazidate were added to the carboxylic acid from Example 60A (5.00 g, 10.4 mmol) in tert-butanol (189 ml), and the mixture was stirred under reflux overnight. The reaction solution was cooled, and the molecular sieves was then filtered off and thoroughly washed with ethyl acetate. The solvent was removed under reduced pressure and the residue was taken up in ethyl acetate. After washing with 2 N aqueous hydrogen chloride solution, saturated aqueous sodium bicarbonate solution and water, the organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. The crude product was used for the next step without further purification. Yield: 5.32 g (70% of theory, purity 71%)

後処理

  1. temperatureunder reflux overnight
  2. temperatureThe reaction solution was cooled
  3. filtrationthe molecular sieves was then filtered off
  4. washthoroughly washed with ethyl acetate
  5. customThe solvent was removed under reduced pressure
  6. washAfter washing with 2 N aqueous hydrogen chloride solution, saturated aqueous sodium bicarbonate solution and water
  7. dry with materialthe organic phase was dried over magnesium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was used for the next step without further purification

出典と根拠

ORDレコード
ord-0d21451275094542bc0b7cc100248547
出典データセット
uspto-grants-2015_03
特許番号
US08987248B2

反応ノート

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