Hydrochloric Acid → 3'-[2-({(4s,5r)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-isopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylic acid

HRID 604659ノート

反応式

HRID 604659 の反応式
[F:1][C:2]([F:50])([F:49])[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:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([O:42]C)=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([CH:45]([CH3:47])[CH3:46])[N:21]=3)[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.O.[OH-].[Li+].Cl>O1CCOCC1.O>[F:50][C:2]([F:1])([F:49])[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:26]4[CH:27]=[C:28]([C:34]5[CH:39]=[CH:38][C:37]([C:40]([OH:42])=[O:41])=[CH:36][C:35]=5[CH3:44])[CH:29]=[CH:30][C:31]=4[O:32][CH3:33])=[CH:24][CH:23]=[C:22]([CH:45]([CH3:47])[CH3:46])[N:21]=3)[C@H:14]2[CH3:48])[CH:6]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:8]=1

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 24969975methyl 3'-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-isopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylate

生成物 1

HCID 249699763'-[2-({(4s,5r)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-isopropylpyridin-3-yl]-4'-methoxy-2-methylbiphenyl-4-carboxylic acid収率 59.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

To a solution of methyl 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-isopropylpyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylate (102 mg, 0.146 mmol) in 1,4-dioxane (3 mL) was added a solution of lithium hydroxide monohydrate (27 mg, 0.643 mmol) in water (1.8 mL). The reaction was stirred for 3 days. The crude mixture was acidified with HCl (aq, 1N, 1 mL). The crude product was purified by reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with a MeCN (0.1% TFA, v/v)/H10 (0.1% TFA, v/v) gradient mixture. Two peaks were recorded in the prep-LC chromatogram representing the desired acid (60 A %, the faster eluting peak) and the starting ester. Corresponding fractions were pooled and evaporated in vacuo to aqueous mixtures. The resulting mixtures were extracted with EtOAc. The separated organic phases were back washed with water, separated, dried over Na2SO4, filtered and evaporated to afford 3′-[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-isopropylpyridin-3-yl]-4′-methoxy-2-methylbiphenyl-4-carboxylic acid (59.27 mg) as a glass and the recovered starting ester. LCMS calc.=686.22; found=687.44 (M+1)+. 1H NMR signals are doubled because of atropoisomerism. 1H NMR (CDCl3, 500 MHz) 8.13 (d, J=8 Hz, 1H), 8.02-7.95 (m, 1H), 7.94-7.88 (m, 1H), 7.85 (s, 1H), 7.70-7.62 (m, 3H), 7.49 (d, J=8.5 Hz, 1H), 7.38 (s, 0.5H), 7.35-7.28 (m, 1H), 7.20-7.10 (m, 1.5H), 5.67 (d, J=7 Hz, 0.7H), 5.58 (d, J=8.0 Hz, 0.3H), 5.05 (d, J=16 Hz, 0.3H), 4.75 (d, J=16 Hz, 0.7H), 4.67 (d, J=16 Hz, 0.7H), 4.60 (d, J=16 Hz, 0.3H), 4.40-4.32 (m, 1H), 3.92 (s, 0.9H), 3.88 (s, 2.1H), 3.74-3.60 (m, 1H), 2.39 (s, 2.1H), 2.35 (s, 0.9H), 1.46 (s, 3H), 1.45 (s, 3H), 0.73 (d, J=6.5 Hz, 2.1H), 0.65 (d, J=5.5 Hz, 0.9H).

後処理

  1. customThe crude product was purified by reverse-phase prep-HPLC (Kromasil 100-5C18, 100×21.1 mm)
  2. washeluting with a MeCN (0.1% TFA, v/v)/H10 (0.1% TFA, v/v) gradient mixture
  3. washfaster eluting peak) and the starting ester
  4. customevaporated in vacuo to aqueous mixtures
  5. extractionThe resulting mixtures were extracted with EtOAc
  6. washThe separated organic phases were back washed with water
  7. customseparated
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated

出典と根拠

ORDレコード
ord-d3f2e77ba0c041039b3f3a7d7fa8b4ca
出典データセット
uspto-grants-2011_03
特許番号
US07910592B2

反応ノート

読み込み中…