Triethylamine → Efavirenz

HRID 389411

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HRID 389411 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C@@]23C(C)(C)[C@@](C)(CC2)C(=O)O3)=[O:10])=[C:4]([C@@:22]([OH:32])([C:27]#[C:28][CH:29]2[CH2:31][CH2:30]2)[C:23]([F:26])([F:25])[F:24])[CH:3]=1.C(N(CC)CC)C.ClC(OC(Cl)C)=O.C([O-])([O-])=O.[K+].[K+]>O.C(OC)(C)(C)C.CN(C)C=O.ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[NH:8][C:9](=[O:10])[O:32][C@:22]([C:27]#[C:28][CH:29]3[CH2:31][CH2:30]3)([C:23]([F:24])([F:25])[F:26])[C:4]=2[CH:3]=1

참가 물질

9

반응물 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 5213051-Chloroethyl chloroformateHCID 50916497(1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide

생성물 1

HCID 64139Efavirenz수율 91.2%

시약·촉매·용매 4

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매HCID 15413tert-Butyl methyl ether용매

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온도
7.5 °C

실험 절차

A solution of (1S,4R)-N-(4-chloro-2-((S)-4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxamide (10, 30 g, 63.9 mmol), dichloromethane (150 mL) and triethylamine (7.11 g, 70.2 mmol) was stirred at 0-5° C. for 20 minutes, then 1-chloroethyl chloroformate (10.0 g, 70.2 mmol) was added dropwise. The mixture was stirred at 5-10° C. for 1 hour. Then N,N-dimethylformamide (150 mL) was added and further evaporated to 220 mL, then K2CO3 (13.3 g, 95.8 mmol) was added. The reaction mixture was stirred at room temperature overnight. Methyl t-butyl ether (300 mL) and water (200 mL) were added to the mixture, and the resulting layers were separated. The organic layer was washed with brine, and concentrated to 60 mL whereupon petroleum ether (200 mL) was added and stirred. The resulting precipitate was filtered and rinsed with petroleum ether to provide 18.4 g (S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one (Efavirenz, 1) as an off-white solid.

후처리

  1. customfurther evaporated to 220 mL
  2. stirringThe reaction mixture was stirred at room temperature overnight
  3. customthe resulting layers were separated
  4. washThe organic layer was washed with brine
  5. concentrationconcentrated to 60 mL whereupon petroleum ether (200 mL)
  6. additionwas added
  7. stirringstirred
  8. filtrationThe resulting precipitate was filtered
  9. washrinsed with petroleum ether

출처 및 근거

ORD 기록
ord-c513ddcaeec444789f3c9e8a7ca2af21
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08378143B2

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