Chlorotrimethylsilane → HCID 58292727, compound

HRID 1798145Notes

Reaction equation

HRID 1798145 reaction equation
Cl[Si](C)(C)C.Br[CH2:7][C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH3:13][C:14]1[CH:21]=[C:20]([O:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:19]=[C:18]([B:29]2[O:33][C:32](C)(C)C(C)(C)[O:30]2)[C:15]=1C=O>C1COCC1.[Zn]>[CH2:11]([O:10][C:8](=[O:9])[CH2:7][CH:32]1[O:33][B:29]([OH:30])[C:18]2[CH:19]=[C:20]([O:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH:21]=[C:14]([CH3:13])[C:15]1=2)[CH3:12]

Participants

6

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 7748Ethyl bromoacetateHCID 58292704HCID 58292704, compound

Product 1

HCID 58292727HCID 58292727, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

A suspension of zinc dust (1.26 g, 19.30 mmol) in THF (8 mL) was treated with chlorotrimethylsilane (0.30 mL, 2.40 mmol) at 40° C. The mixture was heated at 55° C. for 15 minutes, the cooled to 37° C. Ethyl bromoacetate (1.68 mL, 17.70 mmol) was added dropwise (refluxed gently upon addition), then stirred for 5 min. The suspension was allowed to settle at room temperature. The Reformasky reagent (approximately 1.7 M stock solution, 1.5 mL, 2.55 mmol) was transferred via syringe to a dry flask, then cooled to 0° C. 2-Methyl-4-phenoxy-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (0.50 g, 1.48 mmol) in THF (5 mL) was added dropwise to the reagent, then stirred at 0° C. for 4 h. The mixture was quenched with saturated NH4Cl, extracted with EtOAc, dried (Na2SO4), filtered and concentrated to a yellow oil. The oil was purified by column chromatography (SiO2, EtOAc/hexanes; 1:5 to 1:1 gradient) to afford (1-hydroxy-4-methyl-6-phenoxy-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (0.22 g, 46%), as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 7.40 (t, J=7.42 Hz, 2H), 7.16 (t, J=7.42 Hz, 1H), 7.07 (d, J=2.35 Hz, 1H), 7.02-6.97 (m, 3H), 5.51 (dd, J=9.33, 2.34 Hz, 1H), 4.05 (q, J=7.03 Hz, 2H), 3.14 (dd, J=15.63, 2.74 Hz, 1H), 2.89 (s, 3H), 2.33-2.26 (m, 1H), 1.14 (t, J=7.03 Hz, 3H); MS (ES) m/z: 325 (M−1).

Workup

  1. temperaturethe cooled to 37° C
  2. temperaturerefluxed gently upon addition),
  3. customto settle at room temperature
  4. customThe Reformasky reagent (approximately 1.7 M stock solution, 1.5 mL, 2.55 mmol) was transferred via syringe to a dry flask
  5. temperaturecooled to 0° C
  6. stirringstirred at 0° C. for 4 h
  7. customThe mixture was quenched with saturated NH4Cl
  8. extractionextracted with EtOAc
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated to a yellow oil
  12. customThe oil was purified by column chromatography (SiO2, EtOAc/hexanes; 1:5 to 1:1 gradient)

Sources & evidence

ORD record
ord-068ef24930164419a4bf5bf2f828decc
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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