2-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → HCID 178494314, compound

HRID 2095732Notes

Reaction equation

HRID 2095732 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH:19]=[C:18](I)[C:17]([O:21][CH3:22])=[N:16]2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([Mg]Cl)(C)C.CO[B:30]1[O:34][C:33]([CH3:36])([CH3:35])[C:32]([CH3:38])([CH3:37])[O:31]1>C1COCC1>[Si:1]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[CH:19]=[C:18]([B:30]3[O:34][C:33]([CH3:36])([CH3:35])[C:32]([CH3:38])([CH3:37])[O:31]3)[C:17]([O:21][CH3:22])=[N:16]2)[CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 109757592-Methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 178418918HCID 178418918, compoundHCID 178494315HCID 178494315, compound

Product 1

HCID 178494314HCID 178494314, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

A solution of 1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-4-iodo-3-methoxy-1H-pyrazole (0.0500 g, 0.114 mmol) in anhydrous degassed THF (2.0 mL) was cooled to −10° C. and dropwise charged with 1.30 M of isopropylmagnesium chloride in THF (0.352 mL, 0.458 mmol) over a 5 min period under an atmosphere of Argon. The reaction was maintained at −10° C. for 40 min then charged with 2-methoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.0939 mL, 0.573 mmol) and stirred for an additional 1 h at 0° C. The reaction mixture was quenched with sat NH4Cl (2.0 mL) and partitioned between EtOAc and H2O. The aqueous was re-extracted with EtOAc (3×) and the combined organic fractions were washed with brine (1×), dried over Na2SO4, filtered and concentrated in vacuo resulting in a crude yellow oil. The crude was purified by chromatography on silica gel [ISCO Combiflash, 4 g gold cartridge, eluting with 100% heptane→30% EtOAc in heptane] resulting in the title compound as a white waxy solid. 1H NMR (400 MHz, CD3OD): δ=−0.02-0.02 (m, 6H), 0.79-0.84 (m, 9H), 1.19 (s, 12H), 1.32-1.44 (m, 2H), 1.66-1.78 (m, 2H), 1.85-1.92 (m, 2H), 1.94-2.02 (m, 2H), 3.60-3.69 (m, 1H), 3.76-3.79 (m, 3H), 3.86 (tt, J=3.8, 12 Hz, 1H), 7.50 (s, 1H). MS (ES+): m/z 436.27, 437.26, 438.29 [MH+]. HPLC: tR=4.05 min (vvnonpolar—5 min, ZQ3).

Workup

  1. temperatureThe reaction was maintained at −10° C. for 40 min
  2. customThe reaction mixture was quenched with sat NH4Cl (2.0 mL)
  3. custompartitioned between EtOAc and H2O
  4. extractionThe aqueous was re-extracted with EtOAc (3×)
  5. washthe combined organic fractions were washed with brine (1×)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customresulting in a crude yellow oil
  10. customThe crude was purified by chromatography on silica gel [ISCO Combiflash, 4 g gold cartridge, eluting with 100% heptane→30% EtOAc in heptane]

Sources & evidence

ORD record
ord-1113a1133355414495ab1ef48b087809
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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