Hydrochloric Acid → ethyl [(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}thio)-2,3-dihydro-1H-inden-1-yl]acetate

HRID 603515ノート

反応式

HRID 603515 の反応式
CN(C)[C:3]([S:5][C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[C@H:11]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:9]2)=O.[O-:22][CH2:23][CH3:24].[Na+].BrCCC[C:30]1[CH:35]=[CH:34][C:33]([C:36]2[S:37][C:38]3[CH2:44][CH2:43][CH2:42][O:41][C:39]=3[N:40]=2)=[CH:32][C:31]=1[CH2:45][CH2:46][CH3:47].Cl>CN(C=O)C.[Cl-].[Na+].O>[S:37]1[C:38]2[CH2:44][CH2:43][CH2:42][O:41][C:39]=2[N:40]=[C:36]1[C:33]1[CH:34]=[CH:35][C:30]([O:22][CH2:23][CH2:24][CH2:3][S:5][C:6]2[CH:7]=[C:8]3[C:12](=[CH:13][CH:14]=2)[C@H:11]([CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:9]3)=[C:31]([CH2:45][CH2:46][CH3:47])[CH:32]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 2723922Sodium ethoxideHCID 59300457ethyl ((1S)-5-{[(dimethylamino)carbonyl]sulfanyl}-2,3-dihydro-1H-inden-1-yl)acetateHCID 670189722[4-(3-bromopropyl)-3-propylphenyl]-6,7-dihydro-5H-pyrano(2,3-d]thiazole

生成物 1

HCID 86644243ethyl [(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}thio)-2,3-dihydro-1H-inden-1-yl]acetate収率 33.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 57417360Sodium chloride; water溶媒

実験手順

To a solution of ethyl ((1S)-5-{[(dimethylamino)carbonyl]sulfanyl}-2,3-dihydro-1H-inden-1-yl)acetate (130 mg, 0.42 mmol) (Example 508) in DMF (5 mL) was added sodium ethoxide (0.63 mL, 1.69 mmol, 21% solution in EtOH), and the reaction mixture was stirred at rt. The solution turned purple, and after 2 h, the starting material had been consumed. A solution preparation of 2[4-(3-bromopropyl)-3-propylphenyl]-6,7-dihydro-5H-pyrano{2,3-d]thiazole (119 mg, 0.30 mmol) (Example 506) in DMF (1.5 mL) was added. After an additional 2 h of stirring at rt, HCl (4 mL, 1N aqueous solution) was added, followed by brine. The aqueous phase was extracted with ether, and the combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (8:1 hexanes/EtOAc) to give the title compound (55 mg, 33%). 1H NMR (400 MHz, CDCl3) 7.67 (d, 1H), 7.62 (dd, 1H), 7.21 (s, 1H), 7.15 (d, 1H), 7.07 (d, 1H), 6.77 (d, 1H), 4.30 (t, 2H), 4.17 (q, 2H), 4.08 (t, 2H), 3.58-3.48 (m, 1H), 3.11 (t, 2H), 2.92-2.73 (m, 2H), 2.77 (t, 2H), 2.72 (dd, 1H), 2.60 (t, 2H), 2.44-2.32 (m, 2H), 2.16-2.03 (m, 4H), 1.79-1.68 (m, 1H), 1.67-1.57 (m, 2H), 1.28 (t, 3H), 0.94 (t, 3H); LC-MS: RT=4.85 min, (M+H)+ 552.2.

後処理

  1. customthe starting material had been consumed
  2. additionwas added
  3. stirringAfter an additional 2 h of stirring at rt
  4. extractionThe aqueous phase was extracted with ether
  5. dry with materialthe combined organic phases were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography (8:1 hexanes/EtOAc)

出典と根拠

ORDレコード
ord-020efdb3527d4cecbff0bbb0c915a7f5
出典データセット
uspto-grants-2011_03
特許番号
US07906653B2

反応ノート

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