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 1630310ノート

反応式

HRID 1630310 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 LCMS indicated about 70% conversion, so additional 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 (approx 90% coversion) along with small amount of di-acid. Water (20 mL) was then added and the mixture was acidified with 1N HCl (10 mL) and extracted with ether (2×100 mL), washed with brine (50 mL), dried (Na2SO4), filtered and concentrated 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. extractionextracted with ether (2×100 mL)
  4. washwashed with brine (50 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-023685ff4b9c4b39a938c8bb8535af1d
出典データセット
uspto-grants-2014_07
特許番号
US08791108B2

反応ノート

読み込み中…