Tetrahydrofuran → Methyl 2'-fluoro-4-(hydroxymethyl)-5'-(methyloxy)-1,1'-biphenyl-2-carboxylate

HRID 2098916Notes

Reaction equation

HRID 2098916 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16](O)=[O:17])=[CH:12][C:11]=1[C:19]([O:21][CH3:22])=[O:20].C1COCC1.B.C1COCC1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[C:10]1[C:11]([C:19]([O:21][CH3:22])=[O:20])=[CH:12][C:13]([CH2:16][OH:17])=[CH:14][CH:15]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 2723981Borane;tetrahydrofuranHCID 577057642'-Fluoro-5'-(methyloxy)-2-((methyloxy)carbonyl)-1,1'-biphenyl-4-carboxylic acid

Product 1

HCID 57705645Methyl 2'-fluoro-4-(hydroxymethyl)-5'-(methyloxy)-1,1'-biphenyl-2-carboxylateYield 88.3%

Conditions

Temperature
23 °C

Procedure

To a stirred solution of 2′-fluoro-5′-(methyloxy)-2-((methyloxy)carbonyl)-1,1′-biphenyl-4-carboxylic acid T9.4 (35.60 g, 117 mmol) in THF (1170 mL, 117 mmol) at 0° C. was added borane-THF (234 mL, 234 mmol). The reaction was warmed to 23° C. and stirring was continued for 6 hours. The mixture was then concentrated in vacuo. 1 N HCl was added to the reaction, and the mixture was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified on silica gel (0-40% EtOAc in hexane) to give methyl 2′-fluoro-4-(hydroxymethyl)-5′-(methyloxy)-1,1′-biphenyl-2-carboxylate T9.5 as a clear oil (30.00 g, 88% yield). MS ESI (pos.) m/e: 308.0 (M+H2O)+, 291.1 (M+H)+.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. addition1 N HCl was added to the reaction
  3. extractionthe mixture was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on silica gel (0-40% EtOAc in hexane)

Sources & evidence

ORD record
ord-d71b495d48714009ae331e55799e794b
Source dataset
uspto-grants-2013_05
Patent number
US08450522B2

Reaction notes

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