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

HRID 1247488ノート

反応式

HRID 1247488 の反応式
[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

参加物

7

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 702Ethanol溶媒HCID 962Water溶媒HCID 1140Toluene溶媒

実験手順

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)+.

後処理

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

出典と根拠

ORDレコード
ord-2bb35114ca5a4725aff11d82744c2284
出典データセット
uspto-grants-2006_10
特許番号
US07129259B2

反応ノート

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