Sodium Hydroxide → 2,2-Dimethyl-3-(4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propanoic acid

HRID 529352

反応式

HRID 529352 の反応式
FC(F)(F)C([N:5]([C@@H:13]1[CH2:15][C@H:14]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:6][CH:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)=O.[CH3:24][C:25]([CH3:32])([CH:30]=O)[C:26]([O:28]C)=[O:27].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.IC1C=CC=CC=1>[CH3:24][C:25]([CH3:32])([CH2:30][N:10]1[CH2:9][CH2:8][CH:7]([CH2:6][NH:5][C@@H:13]2[CH2:15][C@H:14]2[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:12][CH2:11]1)[C:26]([OH:28])=[O:27]

参加物

7

反応物 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydride2 回HCID 11137194Methyl 2,2-dimethyl-3-oxopropanoate2 回HCID 867082342,2,2-trifluoro-N-((1R,2S)-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide

生成物 1

HCID 683884982,2-Dimethyl-3-(4-((((trans)-2-phenylcyclopropyl)amino)methyl)piperidin-1-yl)propanoic acid

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 11575Iodobenzene溶媒2 回

実験手順

To a solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (130 mg, 0.398 mmol) in 1,2-dichloroethane (DCE) (2 mL) were added methyl 2,2-dimethyl-3-oxopropanoate in iodobenzene (160 mg, 0.478 mmol) and sodium triacetoxyborohydride (118 mg, 0.558 mmol), and the reaction mixture was stirred for 18 h. Additional methyl 2,2-dimethyl-3-oxopropanoate in iodobenzene (320 mg) and sodium triacetoxyborohydride (236 mg) were added and the mixture was stirred at rt for 2 h. The mixture was quenched with water (2 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was dissolved in methanol (2.000 mL) and sodium hydroxide (3M, 0.664 mL, 1.992 mmol) was added. The mixture was stirred at rt for 18 h and concentrated. The residue was treated with methanol and filtered. The filtrate was purified using reverse-phase HPLC under the acidic conditions. The resulting TFA salt was treated with ACN (1 mL) and 1N HCl aqueous solution and concentrated to give 64 mg of product as off-white solid (HCl salt). MS: (M+H)+=311.4. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.19-1.34 (m, 7H), 1.59-1.83 (m, 3H), 1.98 (br. s., 3H), 2.58-2.74 (m, 1H), 2.85-3.24 (m, 7H), 3.42 (br. s., 2H), 7.08-7.43 (m, 5H).

後処理

  1. stirringthe mixture was stirred at rt for 2 h
  2. customThe mixture was quenched with water (2 mL)
  3. extractionextracted with DCM (3×)
  4. dry with materialThe extract was dried (Na2SO4)
  5. concentrationconcentrated
  6. dissolutionThe residue was dissolved in methanol (2.000 mL)
  7. stirringThe mixture was stirred at rt for 18 h
  8. concentrationconcentrated
  9. additionThe residue was treated with methanol
  10. filtrationfiltered
  11. customThe filtrate was purified
  12. additionThe resulting TFA salt was treated with ACN (1 mL) and 1N HCl aqueous solution
  13. concentrationconcentrated

出典と根拠

ORDレコード
ord-fb3e0c215b694b32b6c177fa4300555d
出典データセット
uspto-grants-2016_05
特許番号
US09346840B2

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