Water → Ethyl 2-tert-butoxy-2-(4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate

HRID 514112Notes

Reaction equation

HRID 514112 reaction equation
[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[OH:23])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[B-](F)(F)(F)[F:25].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1.O>CC#N>[C:1]([O:5][CH:6]([C:12]1[C:21]([CH3:22])=[C:20]([F:25])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]=1[OH:23])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 962Water2×HCID 2724933SelectfluorHCID 67126272Ethyl 2-tert-butoxy-2-(1-hydroxy-3-methylnaphthalen-2-yl)acetate

Product 1

HCID 67126298Ethyl 2-tert-butoxy-2-(4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetateYield 79.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
23 °C

Procedure

A solution of ethyl 2-tert-butoxy-2-(1-hydroxy-3-methylnaphthalen-2-yl)acetate (1.50 g, 4.74 mmol) in CH3CN (37.5 mL) was cooled to 0° C. Selectfluor (1.70 g, 4.74 mmol) was added, and the reaction was allowed to warm to 23° C. After 2 h, the reaction was added slowly to a mixture of saturated Na2HPO4 (70 mL) and H2O (30 mL) at 23° C. More H2O (40 mL) was added, and the system was extracted with DCM (3×40 mL). The combined organic phases were treated with hexane (20 mL). The phase that separated was removed. The remaining organic phase was dried (Na2SO4), filtered, and concentrated. The filtrate was concentrated and dissolved in benzene. The solution was wet-loaded onto a 24 g “gold” ISCO silica gel column and purified by flash chromatography (ethyl acetate/hexanes) giving the desired product (1.26 g, 79%). 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 8.23 (d, J=8.2 Hz, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.51 (dd, J=6.9, 6.9 Hz, 1H), 7.45 (dd, J=6.9, 6.9 Hz, 1H), 5.46 (s, 1H), 4.23-4.14 (m, 2H), 2.49 (d, JHF=3.2 Hz, 3H), 1.31 (s, 9H), 1.20 (t, J=7.1 Hz, 3H). 19F NMR (377 MHz, CDCl3) δ−137.3 (app. s).

Workup

  1. extractionthe system was extracted with DCM (3×40 mL)
  2. additionThe combined organic phases were treated with hexane (20 mL)
  3. customThe phase that separated
  4. customwas removed
  5. dry with materialThe remaining organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. concentrationThe filtrate was concentrated
  9. dissolutiondissolved in benzene
  10. custompurified by flash chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-3ea6a8d85ed347e0be3b84cbea2dd849
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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