Hydrochloric Acid → (S)-(4-Fluoro-2-(pent-4-en-2-yloxy)phenyl)boronic acid

HRID 1481999Notes

Reaction equation

HRID 1481999 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[O:9][C@H:10]([CH2:12][CH:13]=[CH2:14])[CH3:11].CC(O)C.C(=O)=O.[Li]CCCC.[B:27](OC(C)C)([O:32]C(C)C)[O:28]C(C)C.Cl>C1COCC1.CCCCCC>[F:8][C:5]1[CH:6]=[CH:7][C:2]([B:27]([OH:32])[OH:28])=[C:3]([O:9][C@H:10]([CH2:12][CH:13]=[CH2:14])[CH3:11])[CH:4]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 21531Triisopropyl borateHCID 86586944Isopropanol carbon dioxideHCID 118308842(S)-1-Bromo-4-fluoro-2-(pent-4-en-2-yloxy)benzeneHCID 178418339Butyllithium

Product 1

HCID 123945833(S)-(4-Fluoro-2-(pent-4-en-2-yloxy)phenyl)boronic acidYield 101.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

A solution of (S)-1-bromo-4-fluoro-2-(pent-4-en-2-yloxy)benzene (0.66 mL, 2.55 mmol, 1 equiv) in THF (13 mL) was cooled to −78° C. (IPA/dry ice). nBuLi (1.9 mL of a 1.6 M solution in hexane, 3.06 mmol, 1.2 equiv) was added slowly. No color change observed. After 45 min, triisopropyl borate (0.70 mL, 3.06 mmol, 1.2 equiv) was added. The reaction was stirred 30 min. 1 N HCl (5 mL) was added and the reaction was removed from the cold bath. After 10 min, the reaction was added to water and extracted with DCM (×3). The combined DCM extracts were dried (Na2SO4) and concentrated in vacuo to provide the crude boronic acid (0.58 g, 100%) as a viscous pale yellow oil. Purity is ˜80%. The crude boronic acid was for used as is for the Suzuki coupling. 1H NMR (500 MHz, CDCl3) δ 7.85 (t, J=8.0 Hz, 1H), 6.74 (td, J=8.3, 2.2 Hz, 1H), 6.66-6.62 (m, 1H), 5.87 (ddt, J=17.1, 10.1, 7.1 Hz, 1H), 5.24-5.18 (m, 2H), 4.63-4.54 (m, 1H), 2.60-2.45 (m, 2H), 1.43 (d, J=6.1 Hz, 3H).

Workup

  1. customthe reaction was removed from the cold bath
  2. waitAfter 10 min
  3. additionthe reaction was added to water
  4. extractionextracted with DCM (×3)
  5. dry with materialThe combined DCM extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-34be0e79eac74340b6d87555486bac02
Source dataset
uspto-grants-2016_08
Patent number
US09409922B2

Reaction notes

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