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Triethylamine → Rac-Efavirenz

HRID 659725
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HRID 659725 반응식
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])C)=[C:4]([C:12]([OH:22])([C:17]#[C:18][CH:19]2[CH2:21][CH2:20]2)[C:13]([F:16])([F:15])[F:14])[CH:3]=1.C(N(CC)CC)C.ClC(OC(Cl)C)=O.C([O-])([O-])=O.[K+].[K+]>O.C1(C)C=CC=CC=1.CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[NH:8][C:9](=[O:11])[O:22][C:12]([C:17]#[C:18][CH:19]3[CH2:20][CH2:21]3)([C:13]([F:16])([F:15])[F:14])[C:4]=2[CH:3]=1
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참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 5213051-Chloroethyl chloroformateHCID 21028954N-(4-chloro-2-(4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)acetamide

생성물 1

HCID 3203Rac-Efavirenz

시약·촉매·용매 3

HCID 962Water
용매
2회
HCID 1140Toluene용매2회
HCID 6228Dimethylformamide용매

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온도
7.5 °C

실험 절차

A solution of N-(4-chloro-2-(4-cyclopropyl-1,1,1-trifluoro-2-hydroxybut-3-yn-2-yl)phenyl)acetamide (5, R1 is methyl, 1.1 g, 3.3 mmol), toluene (5.5 mL) and triethylamine (0.5 mL, 3.65 mmol) was stirred at 0-5° C. under nitrogen then 1-chloroethyl chloroformate (0.52 g, 3.65 mmol) was added dropwise. The mixture was stirred at 5-10° C. overnight. Water (20 mL) was added and the mixture was separated. The organic layer was evaporated to dryness whereupon N,N-dimethyl formamide (5 mL) and K2CO3 (0.9 g, 6.6 mmol) were added. The reaction mixture was stirred at room temperature for 1 day. Toluene (20 mL) and water (20 mL) were added to the mixture, and the resulting mixture was separated. The organic layer was washed with water (20 mL), and evaporated to dryness to give 6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-1H-benzo[d][1,3]oxazin-2(4H)-one as an off-white solid. 1H NMR (CDCl3) δ 9.64 (s, 1H), 7.49 (a, s, 1H), 7.36 (dd, J=8.4, 1.8 Hz, 1H), 6.87 (d, J=8.4 Hz, 1H), 1.43-1.36 (m, 1H), 0.97-0.91 (m, 2H), 0.88-0.86 (m, 2H),

후처리

  1. customthe mixture was separated
  2. additionwere added
  3. stirringThe reaction mixture was stirred at room temperature for 1 day
  4. customthe resulting mixture was separated
  5. washThe organic layer was washed with water (20 mL)
  6. customevaporated to dryness

출처 및 근거

ORD 기록
ord-0ffa65bb38994be09e276d1282a2bafa
출처 데이터셋
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08080655B2

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