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Water → N-((4aS,5S,7aS)-7a-(2,4-Difluorophenyl)-5-(hydroxymethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

HRID 68375
ノート
印刷プレビュー

反応式

HRID 68375 の反応式
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:17][O:16][C@H:15]([CH2:18][O:19]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C@H:14]1[CH2:13][S:12][C:11]([NH:39][C:40](=[O:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[N:10]2.O.C(=O)([O-])[O-].[K+].[K+]>C(O)=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:17][O:16][C@H:15]([CH2:18][OH:19])[C@H:14]1[CH2:13][S:12][C:11]([NH:39][C:40](=[O:47])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)=[N:10]2
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 86707814N-((4aS,5S,7aS)-7a-(2,4-Difluorophenyl)-5-((trityloxy)methyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

生成物 1

HCID 86707815N-((4aS,5S,7aS)-7a-(2,4-Difluorophenyl)-5-(hydroxymethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide収率 89.4%

試薬・触媒・溶媒 1

HCID 284
Formic Acid
溶媒

実験手順

N-((4aS,5S,7aS)-7a-(2,4-Difluorophenyl)-5-((trityloxy)methyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (3.99 g, 6.169 mmol) was taken up in formic acid (12 mL) at RT. The mixture was stirred at RT for 2.5 hours, then water (12 mL) was added. The mixture was stirred for 10 minutes and then filtered—washing with formic acid/water (1:1, 20 mL). The filtrate was evaporated and the residue was azeotroped with toluene (×2). The residue was taken up in dry MeOH (20 mL) and treated with potassium carbonate (1.0 g, 7.2 mmol). The mixture was stirred at RT for 30 minutes. The volatiles were removed in vacuo and the residue was partitioned between DCM and water. The layers were separated and the aqueous layer was further extracted with DCM (×4). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by column chromatography (normal phase, 50 g, Biotage SNAP cartridge KP-Sil, 50 mL per min, gradient 40% to 90% EtOAc in n-hexane) to give the title compound (2.23 g). 1H NMR (400 MHz, MeOH-d4) δ ppm: 2.85-3.05 (m, 1 H) 3.10-3.27 (m, 2 H) 3.68-3.80 (m, 2 H) 4.02 (br. d, J=7.90 Hz, 1 H) 4.36-4.43 (m, 1 H) 4.47 (d, J=9.16 Hz, 1 H) 6.95-7.13 (m, 2 H) 7.39-7.50 (m, 2 H) 7.50-7.60 (m, 2 H) 7.96-8.16 (m, 2 H)

後処理

  1. stirringThe mixture was stirred for 10 minutes
  2. washfiltered—washing with formic acid/water (1:1, 20 mL)
  3. customThe filtrate was evaporated
  4. customthe residue was azeotroped with toluene (×2)
  5. stirringThe mixture was stirred at RT for 30 minutes
  6. customThe volatiles were removed in vacuo
  7. customthe residue was partitioned between DCM and water
  8. customThe layers were separated
  9. extractionthe aqueous layer was further extracted with DCM (×4)
  10. dry with materialThe combined extracts were dried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated
  13. customThe residue was purified by column chromatography (normal phase, 50 g, Biotage SNAP cartridge KP-Sil, 50 mL per min, gradient 40% to 90% EtOAc in n-hexane)

出典と根拠

ORDレコード
ord-f3643d40389f439ab139b6d4d49ca9ee
出典データセット
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08822455B2

反応ノート

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