4-(Dihydroxyboranyl)-3-fluorobenzoic acid → 3-Fluoro-4-(4-fluoro-6-hydroxyquinolin-2-yl)benzoic acid

HRID 628889Notes

Reaction equation

HRID 628889 reaction equation
Cl[C:2]1[CH:11]=[C:10]([F:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13]C)[CH:8]=2)[N:3]=1.[C:15]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[C:20]([F:27])[CH:19]=1)([OH:17])=[O:16]>>[F:27][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[C:2]1[CH:11]=[C:10]([F:12])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([OH:13])[CH:8]=2)[N:3]=1)[C:15]([OH:17])=[O:16]

Participants

3

Reactant 2

HCID 231341774-(Dihydroxyboranyl)-3-fluorobenzoic acidHCID 866899352-Chloro-4-fluoro-6-methoxyquinoline2×

Product 1

HCID 569591993-Fluoro-4-(4-fluoro-6-hydroxyquinolin-2-yl)benzoic acid

Procedure

The compound was prepared following Scheme 2, B conditions starting from 2-chloro-4-fluoro-6-methoxyquinoline (Intermediate 7) and 4-carboxy-2-fluorophenylboronic acid. Note: In step 2, after purification by prep HPLC, the collected fractions were immediately neutralized with sat.NaHCO3 to pH 6, followed by extraction with EtOAc/MeOH (v/v=10/1, 50 mL×3). Combined organics were washed with brine (50 mL), dried over Na2SO4 and concentrated in vacuo to give the desired product. 1H NMR (MeOD 400 MHz): δ 8.10-8.00 (m, 2H), 7.98 (dd, J=8.0, 1.2 Hz, 1H), 7.85 (dd, J=11.6, 1.2 Hz, 1H), 7.62 (dd, J=11.6, 2.0 Hz, 1H), 7.45 (dd, J=9.2, 2.8 Hz, 1H), 7.31 (d, J=2.8 Hz, 1H). MS (ESI): m/z 301.8 [M+H]+.

Workup

  1. customThe compound was prepared
  2. customIn step 2, after purification by prep HPLC
  3. extractionNaHCO3 to pH 6, followed by extraction with EtOAc/MeOH (v/v=10/1, 50 mL×3)
  4. washCombined organics were washed with brine (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f19bd69dc5da4d2e9f25cdd7d87227f7
Source dataset
uspto-grants-2016_04
Patent number
US09315462B2

Reaction notes

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