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Triethylamine → Rac-Efavirenz

HRID 659725
Notes
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Reaction equation

HRID 659725 reaction equation
[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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 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

Product 1

HCID 3203Rac-Efavirenz

Reagents, catalysts & solvents 3

HCID 962
Water
Solvent
2×
HCID 1140TolueneSolvent2×
HCID 6228DimethylformamideSolvent

Conditions

Temperature
7.5 °C

Procedure

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),

Workup

  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

Sources & evidence

ORD record
ord-0ffa65bb38994be09e276d1282a2bafa
Source dataset
uspto-grants-2011_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08080655B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes