Triethylamine → Rac-Efavirenz

HRID 389407Notes

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

Participants

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

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

Sources & evidence

ORD record: ord-952dfd5ce3de417c956355413c47e144
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08378143B2

Reaction notes

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