Potassium Carbonate → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({6-chloro-3-[5-(2-hydroxy-1,1-dimethylethyl)-2-methoxyphenyl]pyridin-2-yl}methyl)-4-methyl-1,3-oxazolidin-2-one

HRID 604642ノート

反応式

HRID 604642 の反応式
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25](Br)=[CH:24][CH:23]=[C:22]([Cl:27])[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]([CH3:43])([CH3:42])[CH2:40][OH:41])=[CH:35][C:34]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.CCOC(C)=O>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:34]4[CH:35]=[C:36]([C:39]([CH3:43])([CH3:42])[CH2:40][OH:41])[CH:37]=[CH:38][C:33]=4[O:32][CH3:31])=[CH:24][CH:23]=[C:22]([Cl:27])[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 575443992-[4-Methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methylpropan-1-olHCID 57576268(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one2 回

生成物 1

HCID 24969645(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({6-chloro-3-[5-(2-hydroxy-1,1-dimethylethyl)-2-methoxyphenyl]pyridin-2-yl}methyl)-4-methyl-1,3-oxazolidin-2-one

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 9) (107.0 mg, 0.207 mmol) and 2-[4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-methylpropan-1-ol (64 mg, 0.207 mmol) in THF (2.3 mL) was added aqueous potassium carbonate (1.6 mL of a 1M solution, 1.6 mmol). The mixture was degassed with nitrogen. While stirring the reaction vigorously at room temperature, 1,1-bis(di-t-butylphosphino)ferrocene palladium chloride (6.7 mg, 0.01 mmol) was added. The reaction was stirred vigorously at room temperature for 15 min, and then diluted with EtOAc (50 mL). The organics were washed with water and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (5 to 50% EtOAc/hexanes) afforded impure product, which was repurified with 1:1:1 CH2Cl2:hexanes:Et2O on silica gel to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({6-chloro-3-[5-(2-hydroxy-1,1-dimethylethyl)-2-methoxyphenyl]pyridin-2-yl}methyl)-4-methyl-1,3-oxazolidin-2-one. Rf=0.29 (40% EtOAc/hexanes). LCMS=616.9 (M+1)+. 1H NMR (CDCl3, 500 MHz, rotamers present) δ 6.94-7.85 (m, 8H), 5.40-5.55 (m, 1H), 4.81-5.08 (m, 1H), 3.54-4.36 (m, 7H), 1.95-2.59 (m, 1H), 1.30-1.34 (m, 6H), 0.62-0.74 (m, 3H).

後処理

  1. customThe mixture was degassed with nitrogen
  2. customthe reaction vigorously at room temperature
  3. stirringThe reaction was stirred vigorously at room temperature for 15 min
  4. washThe organics were washed with water and brine (15 mL each)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by flash chromatography on silica gel (5 to 50% EtOAc/hexanes)
  9. customafforded impure product, which
  10. customwas repurified with 1:1:1 CH2Cl2

出典と根拠

ORDレコード
ord-b7205b0856ef472786e5dbb30a8d1d1c
出典データセット
uspto-grants-2011_03
特許番号
US07910592B2

反応ノート

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