Sodium Hydroxide → (2-Chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)boronic acid

HRID 1473541Notes

Reaction equation

HRID 1473541 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=1.[B:18](OC(C)C)([O:23]C(C)C)[O:19]C(C)C.C([Li])CCC.[OH-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[C:6]([B:18]([OH:23])[OH:19])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 21531Triisopropyl borateHCID 866876002-Chloro-3'-fluoro-4-iodo-5-methoxy-1,1'-biphenylHCID 178418339Butyllithium

Product 1

HCID 86687599(2-Chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)boronic acidYield 66.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A round-bottom flask was charged with 2-chloro-3′-fluoro-4-iodo-5-methoxy-1,1′-biphenyl (1.68 g, 4.63 mmol), triisopropyl borate (1.399 ml, 6.02 mmol), and THF (23.17 ml). The flask was cooled in a dry ice-acetone bath for 10 min, then n-butyllithium (2.5 M in hexane) (2.409 ml, 6.02 mmol) was added drop wise over 1 min. After 40 min, a solution of 2 N aq. NaOH (25 mL) was added. The resulting biphasic mixture was stirred for 10 min, and then partitioned between water and ether. The layers were separated, and the ethereal layer was extracted with water (2×). The combined aq. extracts were washed with ether, and the ethereal layer was back-extracted with water. The combined aq. layers were acidified with 3N aq. HCl (50 mL), and the aq. mixture was extracted with DCM (3×). The combined DCM-layers were dried over sodium sulfate, filtered, and concentrated to give (2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)boronic acid (0.859 g, 3.06 mmol, 66.1% yield) as an oily solid. m/z (ESI) 281.1 (M+H)+.

Workup

  1. temperatureThe flask was cooled in a dry ice-acetone bath for 10 min
  2. custompartitioned between water and ether
  3. customThe layers were separated
  4. extractionthe ethereal layer was extracted with water (2×)
  5. washThe combined aq. extracts were washed with ether
  6. extractionthe ethereal layer was back-extracted with water
  7. extractionthe aq. mixture was extracted with DCM (3×)
  8. dry with materialThe combined DCM-layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-687d740fd2f74024aa26d078ce2cb478
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…