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

HRID 2111936노트

반응식

HRID 2111936 반응식
[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]

참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b8b90998318b4319b1a38f3e24761d41
출처 데이터셋
uspto-grants-2009_04
특허 번호
US07521462B2

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