Isobutylene oxide → 4-{[(2,4-Dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester

HRID 2111936ノート

反応式

HRID 2111936 の反応式
[CH3:1][C:2]1([CH3:5])[CH2:4][O:3]1.Cl([O-])(=O)(=O)=O.[Li+].[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:25][CH2:26][C:27]2[S:31][C:30]([Cl:32])=[N:29][C:28]=2[Cl:33])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(=O)(O)[O-].[Na+]>C(#N)C>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([N:25]([CH2:26][C:27]2[S:31][C:30]([Cl:32])=[N:29][C:28]=2[Cl:33])[CH2:1][C:2]([OH:3])([CH3:5])[CH3:4])[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

参加物

6

反応物 4

HCID 11208Isobutylene oxideHCID 516892Sodium BicarbonateHCID 23665649Lithium perchlorateHCID 685747814-{[(2,4-Dichloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid t-butyl ester

生成物 1

HCID 685774114-{[(2,4-Dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester収率 33.3%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒2 回

実験手順

Add 2,2-dimethyl-oxirane (3.0 mL, 33.3 mmol) to a stirred suspension of lithium perchlorate (3.39 g, 31.9 mmol) in anhydrous acetonitrile (40 mL). Stir for one hour under nitrogen at room temperature. Add 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (1.1337 g, 3.10 mmol) in anhydrous acetonitrile (15 mL). Heat the reaction at reflux for 72 hours under nitrogen. Pour the reaction into saturated sodium bicarbonate (100 mL) and extract with ethyl acetate (3×100 mL). Dry the ethyl acetate over sodium sulfate and then filter off the sodium sulfate. Concentrate on a rotary evaporator and purify the crude product by flash chromatography on silica gel eluting with 30% ethyl acetate/hexanes to yield 0.4527 g (33%) of 4-{[(2,4-dichloro-thiazol-5-yl)methyl]-(2-hydroxy-2-methyl-propyl)-amino}-piperidine-1-carboxylic acid tert-butyl ester: mass spectrum (ion spray): m/z=438.2 (M+1); 1H NMR (CDCl3): δ=4.22 (br s, 2H), 3.97 (s, 2H), 2.67-2.59 (m, 3H), 2.50 (s, 2H), 1.77-1.74 (m, 2H), 1.60 (s, 2H), 1.49 (s, 9H), 1.47-1.35 (m, 1H), 1.23 (s, 6H).

後処理

  1. temperatureHeat
  2. customthe reaction
  3. temperatureat reflux for 72 hours under nitrogen
  4. additionPour
  5. extractionextract with ethyl acetate (3×100 mL)
  6. dry with materialDry the ethyl acetate over sodium sulfate
  7. filtrationfilter off the sodium sulfate
  8. concentrationConcentrate on a rotary evaporator
  9. custompurify the crude product by flash chromatography on silica gel eluting with 30% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-b8b90998318b4319b1a38f3e24761d41
出典データセット
uspto-grants-2009_04
特許番号
US07521462B2

反応ノート

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