Sulfuric Acid → HCID 66748835, compound

HRID 1749156Notes

Reaction equation

HRID 1749156 reaction equation
[C:1]([C:3](=[C:9]1[CH2:12][CH2:11][CH2:10]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2].[C:13]1([Mg]Br)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.OS(O)(=O)=O>CCOCC>[C:1]([CH:3]([C:9]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][CH2:11][CH2:12]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])#[N:2]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 66748801HCID 66748801, compoundHCID 178418255HCID 178418255, compound

Product 1

HCID 66748835HCID 66748835, compoundYield 83.6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of Example 68A (3.0 g, 18.2 mmol) in ether (70 mL) was added dropwise phenyl magnesium bromide (9.0 mL, 3.0 M solution in diethyl ether, 27.4 mmol). The mixture was heated to 60° C. and stirred at this temp for 1 hour after addition was completed. The reaction mixture was cooled to ambient temperature. The resulting dark yellow solution was poured onto crushed ice and the pH was adjusted to about 5-6 with the addition of 20% H2SO4. The mixture was extracted with ethyl acetate/diethyl ether (1:1) (50 mL×2). The combined organic layers were washed with water and brine sequentially, dried over Na2SO4, filtered, and concentrated. The crude product was purified by reserve-phase C18 column chromatography (eluted with H2O/MeOH=1:4) to afford the desired compound (3.7 g, 15.2 mmol, 83.6%). LC-MS: m/e=261.1 (M++18). 1H NMR (400 MHz, CDCl3), 6 (ppm): 7.36-7.23 (m, 5H), 4.00 (q, J=6.8, Hz, J2=14.4 Hz, 2H), 3.91 (s, 1H), 2.80-2.73 (m, 1H), 2.65-2.55 (m, 3H), 2.21-2.07 (m, 1H), 1.99-1.88 (m, 1H), 1.05 (t, J=7.2 Hz, 3H).

Workup

  1. additionafter addition
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. additionThe resulting dark yellow solution was poured
  4. customonto crushed ice
  5. extractionThe mixture was extracted with ethyl acetate/diethyl ether (1:1) (50 mL×2)
  6. washThe combined organic layers were washed with water and brine sequentially
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by reserve-phase C18 column chromatography (eluted with H2O/MeOH=1:4)

Sources & evidence

ORD record
ord-0998a098bfe3402fb0800fd9f05ea000
Source dataset
uspto-grants-2015_10
Patent number
US09156788B2

Reaction notes

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