Hydrochloric Acid → 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid

HRID 1468747ノート

反応式

HRID 1468747 の反応式
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:38])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:33]([O:35]CC)=[O:34])[CH:32]=2)[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].O.Cl>C1COCC1>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:38])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:33]([OH:35])=[O:34])[CH:32]=2)[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium Hydroxide2 回HCID 71258382HCID 71258382、化合物

生成物 1

HCID 712583786-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid収率 89.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of ethyl 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylate (4 g, 6.07 mmol) in THF (40 mL) was added 1N NaOH (6.07 mL, 6.07 mmol) and the resulting mixture was stirred at rt for 16 h. At this point the LCMS indicated about 70% conversion, so additional 1N NaOH (2.5 mL, 2.5 mmol) was added and the mixture was stirred for another 2 h. At this point LCMS indicated progression of reaction (˜90% conversion) along with small amount of di-acid. Water (20 mL) was then added to the reaction mixture and it was acidified with 1N HCl (10 mL). This aqueous solution was extracted with ether (2×100 mL), washed with brine (50 mL), dried (Na2SO4), filtered and concentrated in vacuo to afford 6-((S)-1-(tert-butoxy)-2-ethoxy-2-oxoethyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidine-2-carboxylic acid (2.7 g, 5.41 mmol, 89% yield) as off-white solid. 1H NMR (500 MHz, CDCl3) δ 7.21 (s, 1H), 6.85 (d, J=10.7 Hz, 1H), 5.00 (s, 1H), 4.36 (t, J=4.4 Hz, 2H), 4.19-4.12 (m, 2H), 2.81 (s, 3H), 2.80-2.74 (m, 2H), 2.20 (dd, J=6.3, 4.1 Hz, 2H), 1.83 (s, 3H), 1.24-1.20 (m, 3H), 1.18 (s, 9H). LCMS (M+H)=500.4.

後処理

  1. additionwas added
  2. stirringthe mixture was stirred for another 2 h
  3. extractionThis aqueous solution was extracted with ether (2×100 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-be5d832a67f744b383d9182c725c732c
出典データセット
uspto-grants-2015_04
特許番号
US09006235B2

反応ノート

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