Trimethyl borate → (4-Chloro-2,5-difluorophenyl)methanol

HRID 1977847Notes

Reaction equation

HRID 1977847 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6](O)=[O:7])=[C:4]([F:12])[CH:3]=1.COB(OC)OC.B.CSC.[OH-].[Na+]>>[Cl:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([CH2:6][OH:7])=[C:4]([F:12])[CH:3]=1

Participants

5

Reactant 4

HCID 8470Trimethyl borateHCID 14798Sodium HydroxideHCID 27332744-Chloro-2,5-difluorobenzoic acidHCID 12423031(Dimethyl sulfide)trihydroboron

Product 1

HCID 18550157(4-Chloro-2,5-difluorophenyl)methanolYield 100.5%

Procedure

To a mixture of 4-chloro-2,5-difluoro-benzoic acid (15 g, 78 mmol) tetrahydrofuran (THF) (75 mL) and trimethylborate (26 mL, 230 mmol) was added borane-methylsulfide complex (86 mL, 86 mmol, 10 M solution in DMS), and the mixture was stirred for 18 hours at ambient temperature. Additional borane-methylsulfide complex (2.47 mL, 24.7 mmol) was added to drive the reaction to completion. The mixture was poured into 1M aqueous NaOH, extracted 3× with ether, and the combined organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo. Trituration of the solid residue with ether-hexane afforded 14 g of (4-chloro-2,5-difluoro-phenyl)-methanol as a colorless solid. 1H NMR (400 MHz, CDCl3) δ7.26 (dd, 1H, J=6, 8.8 Hz), 7.11 (dd, 1H, J=6, 9.2 Hz), 4.71 (d, 2H, J=6.0 Hz), 1.80 (t, 1H, J=6.0 Hz) ppm.

Workup

  1. additionAdditional borane-methylsulfide complex (2.47 mL, 24.7 mmol) was added
  2. customthe reaction to completion
  3. extractionextracted 3× with ether
  4. dry with materialthe combined organic layers were dried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-decc5dffba6c4bb29501cfeaefc0e5d7
Source dataset
uspto-grants-2001_05
Patent number
US06235764B1

Reaction notes

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