4-(Hydroxymethyl)benzeneboronic acid → 3-(2-Fluoro-4'-hydroxymethyl-biphenyl-4-yl)-5-(isoxazol-3-yloxymethyl)-oxazolidin-2-one

HRID 1247488Notes

Reaction equation

HRID 1247488 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][CH:12]([CH2:14][O:15][C:16]3[CH:20]=[CH:19][O:18][N:17]=3)[O:11][C:10]2=[O:21])[CH:5]=[CH:6][C:7]=1I.[OH:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1>C1(C)C=CC=CC=1.CCO.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[CH2:13][CH:12]([CH2:14][O:15][C:16]3[CH:20]=[CH:19][O:18][N:17]=3)[O:11][C:10]2=[O:21])[CH:5]=[CH:6][C:7]=1[C:27]1[CH:28]=[CH:29][C:24]([CH2:23][OH:22])=[CH:25][CH:26]=1

Participants

7

Reactant 2

HCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 219074133-(3-Fluoro-4-iodo-phenyl)-5-(isoxazol-3-yloxymethyl)-oxazolidin-2-one

Product 1

HCID 219074803-(2-Fluoro-4'-hydroxymethyl-biphenyl-4-yl)-5-(isoxazol-3-yloxymethyl)-oxazolidin-2-one

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A degassed mixture containing 3-(3-fluoro-4-iodo-phenyl)-5-(isoxazol-3-yloxymethyl)-oxazolidin-2-one (1.0 g, 2.48 mmol), 4-(hydroxymethyl)phenylboronic acid (0.46 g, 3.00 mmol) and Pd(PPh3)4 in toluene (24 mL), EtOH (8 mL) and H2O (8 mL) was heated to reflux for 15 h. The reaction was concentrated, the crude residue was suspended in H2O, filtered and dried in vacuo to give 3-(2-fluoro-4′-hydroxymethyl-biphenyl-4-yl)-5-(isoxazol-3-yloxymethyl)-oxazolidin-2-one. This crude material was dissolved in CH2Cl2 (10 mL) and Hunig's base (0.88 mL, 5.3 mmol), then MsCl (0.32 mL, 2.65 mmol) was added and the mixture was stirred at room temperature for 15 h. The reaction was partitioned between dilute sodium bicarbonate (NaHCO3, 20 mL) and CH2Cl2 (30 mL). The two layers were separated and the organic phase was washed with saturated ammonium chloride (NH4Cl, 1×20 mL) and H2O (1×20 mL) and dried over Na2SO4. The solvent was evaporated and the crude was purified on silica gel eluting with 0–3% MeOH in CH2Cl2 to give benzyl chloride 107 as white crystalline solid (0.46 g; 43% yield over the last two steps). LCMS (ESI) m/z 403 (M+H)+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 15 h
  3. concentrationThe reaction was concentrated
  4. filtrationfiltered
  5. customdried in vacuo

Sources & evidence

ORD record
ord-2bb35114ca5a4725aff11d82744c2284
Source dataset
uspto-grants-2006_10
Patent number
US07129259B2

Reaction notes

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