Sodium Iodide → Acetyl-{(R)-3-[3-fluoro-4-(2-methyl-2,6-dihydro-4H-pyrrolo[3,4-c]pyrazol-5-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-carbamic acid 1-(di-tert-butoxy-phosphoryloxy)-ethyl ester

HRID 502532ノート

反応式

HRID 502532 の反応式
Cl[CH:2]([O:4][C:5](=[O:33])[N:6]([C:30](=[O:32])[CH3:31])[CH2:7][C@@H:8]1[O:12][C:11](=[O:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:27][C:26]4[C:22](=[N:23][N:24]([CH3:28])[CH:25]=4)[CH2:21]3)=[C:16]([F:29])[CH:15]=2)[CH2:9]1)[CH3:3].[I-].[Na+].[C:36]([O:40][P:41]([O-:48])([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])([CH3:39])([CH3:38])[CH3:37]>C1COCC1>[C:36]([O:40][P:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])([O:48][CH:2]([O:4][C:5](=[O:33])[N:6]([C:30](=[O:32])[CH3:31])[CH2:7][C@@H:8]1[O:12][C:11](=[O:13])[N:10]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:27][C:26]4[C:22](=[N:23][N:24]([CH3:28])[CH:25]=4)[CH2:21]3)=[C:16]([F:29])[CH:15]=2)[CH2:9]1)[CH3:3])=[O:42])([CH3:39])([CH3:38])[CH3:37]

参加物

5

反応物 3

HCID 5238Sodium IodideHCID 4191557Ditert-butyl phosphateHCID 68465837Acetyl-{(R)-3-[3-fluoro-4-(2-methyl-2,6-dihydro-4H-pyrrolo[3,4-c]pyrazol-5-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-carbamic acid 1-chloro-ethyl ester

生成物 1

HCID 68464915Acetyl-{(R)-3-[3-fluoro-4-(2-methyl-2,6-dihydro-4H-pyrrolo[3,4-c]pyrazol-5-yl)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-carbamic acid 1-(di-tert-butoxy-phosphoryloxy)-ethyl ester収率 76.5%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
65 °C

実験手順

To a solution of 2b (75 mg, 0.16 mmol) in THF (1.5 mL) was added sodium iodide (66 mg, 0.44 mmol) and the tetrabutylammonium salt of di-tert-butylphosphate (200 mg, 0.04 mmol). The reaction mixture was heated at 65° C. for 48 h, concentrated in vacuo, dissolved in DMSO, filtered, and purified directly by HPLC (C-18 column, 30-100% gradient elution, MeCN:H2O). Fractions containing product were lyophilized to give 20 mg (20%) of the title compound as a 1:1 mixture of diastereomers. 1H NMR (400 MHz, DMSO-d6): δ 7.53 (s, 1H), 7.44-7.39 (m, 1H), 7.17-7.14 (m, 1H), 6.90-6.85 (m, 1H), 6.45-6.38 (m, 1H), 4.85-4.75 (m, 1H), 4.48-4.46 (m, 4H), 4.25-4.08 (m, 2H), 3.95-3.77 (m, 2H), 3.85 (s, 3H), 2.47-2.48 (m, 3H), 1.56-1.54 (m, 3H), 1.41-1.40 (m, 18H). MS 654 (M+1)+

後処理

  1. concentrationconcentrated in vacuo
  2. dissolutiondissolved in DMSO
  3. filtrationfiltered
  4. custompurified directly by HPLC (C-18 column, 30-100% gradient elution, MeCN:H2O)
  5. additionFractions containing product

出典と根拠

ORDレコード
ord-40d64b75c56d4155b5c6ffa9a519788e
出典データセット
uspto-grants-2010_08
特許番号
US07776855B2

反応ノート

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