Tetrahydrofuran → 1-(2'-Fluoro-4-(hydroxymethyl)-5'-(methyloxy)-1,1'-biphenyl-2-yl)-2,2-dimethyl-1-propanone

HRID 1662385Notes

Reaction equation

HRID 1662385 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[C:11]([C:18]([O:20]C)=O)=[CH:12][C:13]([CH2:16][OH:17])=[CH:14][CH:15]=1.C1COCC1.[C:27]([Li])([CH3:30])([CH3:29])[CH3:28].[Cl-].[NH4+]>>[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]([CH2:16][OH:17])=[CH:12][C:11]=1[C:18](=[O:20])[C:27]([CH3:30])([CH3:29])[CH3:28]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 57705645Methyl 2'-fluoro-4-(hydroxymethyl)-5'-(methyloxy)-1,1'-biphenyl-2-carboxylateHCID 178418306HCID 178418306, compound

Product 1

HCID 574675911-(2'-Fluoro-4-(hydroxymethyl)-5'-(methyloxy)-1,1'-biphenyl-2-yl)-2,2-dimethyl-1-propanoneYield 92%

Procedure

To a stirred solution of methyl 2′-fluoro-4-(hydroxymethyl)-5′-(methyloxy)-1,1′-biphenyl-2-carboxylate 66.13E (2.00 g, 7 mmol) in THF (138 mL, 7 mmol) at −78° C. was added t-butyllithium (1.7 M in pentane, 9 mL, 14 mmol). Stirring was continued for 3 hours. A saturated solution of ammonium chloride was added to quench the reaction, and the resulting mixture was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give the crude product. The crude product was purified by silica gel flash chromatography (0-20% EtOAc/hexane) to afford 1-(2′-Fluoro-4-(hydroxymethyl)-5′-(methyloxy)-1,1′-biphenyl-2-yl)-2,2-dimethyl-1-propanone 66.13F as a clear oil (2.00 g, 92% yield). MS ESI (pos.) m/e: 334.1 (M+H2O)+, 317.2 (M+H)+.

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe resulting mixture was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give the crude product
  8. customThe crude product was purified by silica gel flash chromatography (0-20% EtOAc/hexane)

Sources & evidence

ORD record
ord-0931b8405dc24988aedd727717d40f16
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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