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Lithium Hydroxide → 6-{(S)-2-[4-(2-chloro-6-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionylamino}-nicotinic acid

HRID 19008
ノート
印刷プレビュー

反応式

HRID 19008 の反応式
C[O:2][C:3](=[O:36])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:35])[C@@H:12]([N:20]2[CH2:24][C:23]([O:25][C:26]3[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=3[Cl:33])=[CH:22][C:21]2=[O:34])[CH2:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[N:6][CH:5]=1.[OH-].[Li+]>O1CCCC1.C(OCC)(=O)C>[Cl:33][C:27]1[CH:28]=[CH:29][CH:30]=[C:31]([F:32])[C:26]=1[O:25][C:23]1[CH2:24][N:20]([C@@H:12]([CH2:13][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:36])=[O:2])=[CH:5][N:6]=2)=[O:35])[C:21](=[O:34])[CH:22]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 2

HCID 3939Lithium HydroxideHCID 442517366-{(S)-2-[4-(2-chloro-6-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionylamino}-nicotinic acid methyl ester

生成物 1

HCID 442517376-{(S)-2-[4-(2-chloro-6-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionylamino}-nicotinic acid収率 13%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒
HCID 8857
Ethyl Acetate
溶媒

反応条件

温度
25 °C

実験手順

To a magnetically stirred mixture of 6-{(S)-2-[4-(2-chloro-6-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionylamino}-nicotinic acid methyl ester (prepared as in Example 69, 80 mg, 0.16 mmol) in tetrahydrofuran (3.0 mL) was added 0.5N lithium hydroxide solution (1.0 mL, 0.5 mmol). After addition was complete the mixture was stirred at 25° C. for 4 h. The reaction mixture was diluted with ethyl acetate, washed with 1N aqueous hydrochloric acid, water, a saturated sodium chloride solution and dried over sodium sulfate. The crude product was recrystallized from ethyl acetate to afford 6-{(S)-2-[4-(2-chloro-6-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionylamino}-nicotinic acid (10 mg, 13%) as a white solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 0.73-1.42 (m, 6H) 1.41-1.90 (m, 7H) 4.28 (d, J=18.7 Hz, 1H) 4.64 (d, J=18.7 Hz, 1H) 4.99 (s, 1H) 5.01-5.10 (m, 1H) 7.31-7.57 (m, 3H) 8.14 (d, J=8.5 Hz, 1H) 8.25 (dd, J=8.5, 2.1 Hz, 1H) 8.84 (d, J=2.1 Hz, 1H) 11.26 (s, 1H) 13.18 (br. s., 1H). HR-ES-MS m/z calculated for C25H25ClFN3O5 [M+H]+ 502.1540, observed 502.1537.

後処理

  1. additionAfter addition
  2. washwashed with 1N aqueous hydrochloric acid, water
  3. dry with materiala saturated sodium chloride solution and dried over sodium sulfate
  4. customThe crude product was recrystallized from ethyl acetate

出典と根拠

ORDレコード
ord-7d9a9181fa8440108234d939b3eb3700
出典データセット
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07741327B2

反応ノート

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