Phenol → HCID 58388876, compound

HRID 626321Notes

Reaction equation

HRID 626321 reaction equation
C(OC(C)C)(=O)C.[Si:8]([O:15][C:16]1[C:17]([CH3:26])=[C:18]([CH:23]=[CH:24][CH:25]=1)[C:19]([O:21][CH3:22])=[O:20])([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9].C1(O)C=CC=CC=1.[Br:34]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>>[Br:34][CH2:26][C:17]1[C:16]([O:15][Si:8]([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:9])[CH3:10])=[CH:25][CH:24]=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20]

Participants

6

Reactant 5

HCID 996PhenolHCID 6547AzobisisobutyronitrileHCID 7915Isopropyl Acetate2×HCID 67184N-bromobutanimide2×HCID 19597156HCID 19597156, compound

Product 1

HCID 58388876HCID 58388876, compoundYield 90%

Conditions

Temperature
70 °C

Procedure

The isopropyl acetate solution of methyl 3-((tert-butyldimethylsilyl)oxy)-2-methylbenzoate (157 g, 560 mmol, from step 2, with an amount of residue free phenol≦0.2%) was added to a 3 liter jacketed bottom drop reactor. Additional isopropyl acetate was added and the mixture was distilled under vacuum at 40 to 55° C., if necessary, to bring total volume to about 9× (1410 mL, KF≦0.05%). 1-Bromopyrrolidine-2,5-dione (NBS, 103.6 g, 580 mmol, 0.66×) and 2,2′-(diazene-1,2-diyl)bis(2-methylpropanenitrile) (AIBN, 1.9 g, 11 mmol, 0.012×) were added to the solution. The reaction mixture was heated to 70° C. over at least 2 hours and stirred at 70° C. for 2 hours. The color changed from orange to yellow. If conversion was less than 95%, additional 0.05 molar equiv. of NBS was added and the mixture was stirred at 70° C. for 1 hour. The process was repeated, in necessary, until conversion reached 95%. The mixture was cooled to 20° C. and held at 20° C. for at least 1 hour. The solid (succinimide) was filtered and washed with isopropyl acetate (75 mL, 0.5×). The filtrate was washed with solution of sodium sulfite (157 g, 1×) in water (1413 mL, 9×), followed by water (315 mL, 2×). The organic layer was distilled under vacuum at 30 to 40° C. to ˜2× volume. Additional isopropyl acetate (315 mL, 2×) was added and distilled back to 2× volume, if necessary, until KF was no more than 0.1%. Then the organic layer was distilled at 30 to 40° C. to give methyl 2-(bromomethyl)-3-((tert-butyldimethylsilyl)oxy)benzoate as an oil (expected 180 g, 90% yield); 1H NMR (DMSO-d6, 300 MHz) δ 7.47 (dd, J=7.8, 1.2 Hz, 1H), 7.37 (t, J=8.1 Hz, 1H), 7.15 (dd, J=8.1, 1.2 Hz, 1H), 4.96 (s, 2H), 3.86 (s, 3H), 1.03 (s, 9H), 0.30 (s, 6H) ppm.

Workup

  1. distillationthe mixture was distilled under vacuum at 40 to 55° C.
  2. stirringthe mixture was stirred at 70° C. for 1 hour
  3. temperatureThe mixture was cooled to 20° C.
  4. waitheld at 20° C. for at least 1 hour
  5. filtrationThe solid (succinimide) was filtered
  6. washwashed with isopropyl acetate (75 mL, 0.5×)
  7. washThe filtrate was washed with solution of sodium sulfite (157 g, 1×) in water (1413 mL, 9×)
  8. distillationThe organic layer was distilled under vacuum at 30 to 40° C. to ˜2× volume
  9. additionAdditional isopropyl acetate (315 mL, 2×) was added
  10. distillationdistilled back to 2× volume
  11. distillationThen the organic layer was distilled at 30 to 40° C.

Sources & evidence

ORD record
ord-d0b93997e4a34903903ef5878245d947
Source dataset
uspto-grants-2016_04
Patent number
US09309220B2

Reaction notes

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