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Triethylamine → Rac-Efavirenz

HRID 659725
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 659725
[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
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 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

Produkt 1

HCID 3203Rac-Efavirenz

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962
Water
Lösungsmittel
2×
HCID 1140TolueneLösungsmittel2×
HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
7.5 °C

Versuchsvorschrift

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),

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-0ffa65bb38994be09e276d1282a2bafa
Quelldatensatz
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08080655B2

Notizen zur Reaktion

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