Lithium Hydroxide → 4-(4-(3-Cyclohexylpropoxy)-2-oxopyridin-1(2h)-yl)-2-methyl-2-(methylsulfonyl)butanoic acid

HRID 709295ノート

反応式

HRID 709295 の反応式
[OH:1][C:2]1[CH:7]=[CH:6][N:5]([CH2:8][CH2:9][C:10]([CH3:20])([S:16]([CH3:19])(=[O:18])=[O:17])[C:11]([O:13]CC)=[O:12])[C:4](=[O:21])[CH:3]=1.[CH:22]1([CH2:28][CH2:29][CH2:30]O)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Li+].[OH-]>C(OCC)(=O)C.O.C1COCC1>[CH:22]1([CH2:28][CH2:29][CH2:30][O:1][C:2]2[CH:7]=[CH:6][N:5]([CH2:8][CH2:9][C:10]([CH3:20])([S:16]([CH3:19])(=[O:17])=[O:18])[C:11]([OH:13])=[O:12])[C:4](=[O:21])[CH:3]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

参加物

9

反応物 5

HCID 3939Lithium HydroxideHCID 11776TriphenylphosphineHCID 707633-Cyclohexyl-1-propanolHCID 5363146Diisopropyl azodicarboxylateHCID 67248478Ethyl 4-(4-hydroxy-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate

生成物 1

HCID 672616014-(4-(3-Cyclohexylpropoxy)-2-oxopyridin-1(2h)-yl)-2-methyl-2-(methylsulfonyl)butanoic acid収率 51.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Ethyl 4-(4-hydroxy-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)butanoate (285 mg, 0.898 mmol) was weighed into a 20 ml septa cap vial with THF (10 ml) added. To this was added 3-cyclohexyl-1-propanol (0.191 ml, 1.26 mmol), followed by triphenylphosphine (330 mg, 1.21 mmol). The reaction mixture was stirred at RT for 20 minutes and then DIAD (0.248 ml, 1.26 mmol) was added. The reaction mixture was stirred for 72 hours at RT, was then diluted with ethyl acetate (100 ml) and washed with saturated sodium bicarbonate (50 ml). The product was re-extracted with ethyl acetate (100 ml). The organic phases were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dissolved in dioxane (6 ml) and ethanol (6 ml). To this was added a 2.0M aqueous solution of LiOH (2.6 ml, 5.3 mmol). The reaction mixture was stirred at RT overnight, then was diluted with 30 ml of water and washed with ethyl acetate (2×50 ml) to remove any TPPO. The aqueous phase was adjusted to pH-2 with 1N HCl (10 ml) and the product was extracted with ethyl acetate (3×50 ml). The organic phases were combined, dried over sodium sulfate, filtered and concentrated to provide the title compound as a white solid (190 mg, 51%). MS (LC/MS) m/z 414.1 (M+1)1H NMR (400 MHz, METHANOL-d4) δ ppm 0.81-1.08 (m, 2H) 1.16-1.44 (m, 6H) 1.72 (s, 9H) 2.01 (s, 1H) 2.29-2.47 (m, 1H) 2.48-2.68 (m, 1H) 3.18 (s, 3H) 4.04 (s, 2H) 4.07-4.17 (m, 1H) 4.22-4.37 (m, 1H) 5.97-6.12 (m, 1H) 6.25-6.36 (m, 1H) 7.57-7.73 (m, 1H)

後処理

  1. additionadded
  2. stirringThe reaction mixture was stirred for 72 hours at RT
  3. washwashed with saturated sodium bicarbonate (50 ml)
  4. extractionThe product was re-extracted with ethyl acetate (100 ml)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in dioxane (6 ml)
  9. stirringThe reaction mixture was stirred at RT overnight
  10. washwashed with ethyl acetate (2×50 ml)
  11. customto remove any TPPO
  12. extractionthe product was extracted with ethyl acetate (3×50 ml)
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated

出典と根拠

ORDレコード
ord-59a3b03316204349b38d4ce17d8fc87b
出典データセット
uspto-grants-2015_11
特許番号
US09180123B2

反応ノート

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