Hydrochloric Acid → HCID 13732851, compound

HRID 1731815Notes

Reaction equation

HRID 1731815 reaction equation
[C:1]1([Li])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[F:8][C:9]1[C:10](Br)=[C:11]2[O:16][CH2:15][CH:14]([CH3:17])[N:13]3[CH:18]=[C:19]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:20](=[O:23])[C:21]([CH:22]=1)=[C:12]23.Cl>O1CCCC1>[F:8][C:9]1[C:10]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[C:11]2[O:16][CH2:15][CH:14]([CH3:17])[N:13]3[CH:18]=[C:19]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:20](=[O:23])[C:21]([CH:22]=1)=[C:12]23

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 13732847HCID 13732847, compoundHCID 178506676HCID 178506676, compound

Product 1

HCID 13732851HCID 13732851, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of phenyl lithium (2.7M) in etherbenzene [(3:7), 1.5 ml, 4 mmol] was added to dry tetrahydrofuran (10 ml) and the resulting solution was cooled to -78° C. with stirring under a nitrogen atmosphere. A solution of freshly fused zinc chloride (0.54 g, 4 mmol) in dry tetrahydrofuran (10 ml) was added dropwise over 5 minutes. The clear, colorless solution was warmed to -30° C. over 20 minutes. Ethyl 9-fluoro-10-bromo-3-methyl-7-oxo-2,3-dihydro-(7H)-pyrido-(1,2,3-de)-1,4-benzoxazine-6-carboxylate (1.0 g, 2.7 mmol) was added in one portion; then dichlorobis(triphenylphosphine) nickel (0.13 g, 0.2 mmol) was added in one portion. The reaction mixture was gradually warmed to ambient temperature and stirred for 24 hours. The dark brown mixture was poured onto a 1N hydrochloric acid solution (100 ml) and the aqueous mix was stirred for 15 minutes. Three extractions with chloroform (50 ml), drying the combined organic layers over magnesium sulfate, treatment with decolorizing charcoal and filtration through diatomaceous earth gave a yellow solution. Removal of solvent in vacuo afforded a bright yellow solid. Trituration with ether, filtration and drying in vacuo gave a pale yellow solid (0.67 g, 46% yield): m.p. 270°-272° C. NMR (CDCl3, 250 MHz): 8.42 (s, 1H), 7.85 (d, 1H, J=10 Hz), 7.55-7.40 (m, 5H), 4.42 (q, 2H, J=7 Hz), 4.50-4.35 (m, 3H), 1.62 (d, 3H, J=8 Hz), 1.45 (t, 3H, J=7 Hz).

Workup

  1. temperatureThe clear, colorless solution was warmed to -30° C. over 20 minutes
  2. temperatureThe reaction mixture was gradually warmed to ambient temperature
  3. stirringstirred for 24 hours
  4. additionthe aqueous mix
  5. stirringwas stirred for 15 minutes
  6. extractionThree extractions with chloroform (50 ml)
  7. dry with materialdrying the combined organic layers over magnesium sulfate, treatment
  8. filtrationwith decolorizing charcoal and filtration through diatomaceous earth
  9. customgave a yellow solution
  10. customRemoval of solvent in vacuo
  11. customafforded a bright yellow solid
  12. filtrationTrituration with ether, filtration
  13. customdrying in vacuo

Sources & evidence

ORD record
ord-d93bb4a8f90b40d3ab66249b78b50896
Source dataset
uspto-grants-1986_11
Patent number
US04623650

Reaction notes

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