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

HRID 603516ノート

反応式

HRID 603516 の反応式
[S:1]1[C:5]2[CH2:6][CH2:7][CH2:8][O:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:35]=[CH:34][C:13]([O:14][CH2:15][CH2:16][CH2:17][S:18][C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[C@H:24]([CH2:28][C:29]([O:31]CC)=[O:30])[CH2:23][CH2:22]3)=[C:12]([CH2:36][CH2:37][CH3:38])[CH:11]=1.C(O)C.[Li+].[OH-].Cl>C1COCC1.O>[S:1]1[C:5]2[CH2:6][CH2:7][CH2:8][O:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:35]=[CH:34][C:13]([O:14][CH2:15][CH2:16][CH2:17][S:18][C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[C@H:24]([CH2:28][C:29]([OH:31])=[O:30])[CH2:23][CH2:22]3)=[C:12]([CH2:36][CH2:37][CH3:38])[CH:11]=1

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 3939Lithium HydroxideHCID 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

生成物 1

HCID 10481902[(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}sulfanyl)-2,3-dihydro-1H-inden-1-yl]acetic acid収率 38.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of ethyl [(1S)-5-({3-[4-(6,7-dihydro-5H-pyrano[2,3-d][1,3]thiazol-2-yl)-2-propylphenoxy]propyl}sulfanyl)-2,3-dihydro-1H-inden-1-yl]acetate (50 mg, 0.09 mmol) (Example 509) in a mixture of THF (2 mL), ethanol (1 mL), and water (2 mL) was added LiOH (8.7 mg, 0.36 mmol). The reaction mixture was stirred vigorously at rt for 18 h, and then it was acidified to pH ˜2 using HCl (1M aqueous solution). The aqueous phase was extracted with CH2Cl2, and the combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (4:1 hexanes/EtOAc) to give the title compound (18 mg, 38%) as a white solid. 1H NMR (400 MHz, CDCl3) 7.64 (d, 1H), 7.62 (dd, 1H), 7.22 (s, 1H), 7.15 (d, 1H), 7.08 (d, 1H), 6.75 (d, 1H), 4.31 (t, 2H), 4.15-4.05 (m, 2H), 3.58-3.50 (m, 1H), 3.12 (t, 2H), 2.93-2.80 (m, 2H), 2.78 (t, 2H), 2.78-2.73 (m, 1H), 2.60 (t, 2H), 2.49 (dd, 1H), 2.45-2.36 (m, 1H), 2.17-2.06 (m, 4H), 1.81-1.73 (m, 1H), 1.68-1.58 (m, 2H), 0.95 (t, 3H); LC-MS: RT=4.54 min, (M+H)+ 524.2.

後処理

  1. extractionThe aqueous phase was extracted with CH2Cl2
  2. dry with materialthe combined organic phases were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel flash chromatography (4:1 hexanes/EtOAc)

出典と根拠

ORDレコード
ord-5f0fa2ecfa924b52bcd9964aa7b0ae56
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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