Dimethyl Sulfate → 7-Fluoro-1-methylindolin-2-one

HRID 2114866Notes

Reaction equation

HRID 2114866 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8](=[O:11])[CH2:7]2.[OH-].[Na+].S(OC)(O[CH3:18])(=O)=O>O>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH3:18])[C:8](=[O:11])[CH2:7]2

Participants

5

Reactant 3

HCID 6497Dimethyl Sulfate2×HCID 14798Sodium Hydroxide2×HCID 37343717-Fluoro-2,3-dihydro-1h-indol-2-one

Product 1

HCID 119516747-Fluoro-1-methylindolin-2-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

This is similar to the procedure described in G. W. Rewcastle, B. D. Palmer, E. M. Dobrusin, D. W. Fry, A. J. Kracker and W. A. Deny, Journal of Medicinal Chemistry, 1994, 37, 2033-2042. A suspension of the 7-fluoro-1,3-dihydro-indol-2-one (9, 1.0 g, 6.62 mmol.) in H2O (30 mL) and NaOH (0.397 g, 9.92 mmol., 1.50 eq.) was treated with dimethyl sulfate (1.24 g, 9.86 mmol., 1.49 eq., 0.933 mL; added all at once) and heated to 100° C. for approx. 10 min. and then allowed to cooled to about 50° C. An additional 1.0 eq. of NaOH (0.265 g) and then additional 1 eq. of dimethyl sulfate (0.835 g, 0.626 mL) were added. Again heated to 100° for approx. 10 min. Then cooled to 0° C. in an ice bath and stirred and then filtered off solids, washed several times with water and dried on buchner funnel under vacuum overnight to yield the title compound as a solid. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 3.4 (d, J=2.5 Hz, 3H) 3.5 (s, 2H) 6.9 (m, 3H).

Workup

  1. additionadded all at once) and
  2. temperatureto cooled to about 50° C
  3. temperatureAgain heated to 100° for approx. 10 min
  4. temperatureThen cooled to 0° C. in an ice bath
  5. filtrationfiltered off solids
  6. washwashed several times with water
  7. customdried on buchner funnel under vacuum overnight

Sources & evidence

ORD record
ord-0c068bd5607345a6ba26ebf4a30a7b3e
Source dataset
uspto-grants-2008_10
Patent number
US07435751B2

Reaction notes

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