Sodium Hydroxide → 4-((2-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)morpholino)methyl)benzoic acid

HRID 529383ノート

反応式

HRID 529383 の反応式
FC(F)(F)C([N:5]([CH2:15][CH:16]1[O:21][CH2:20][CH2:19][NH:18][CH2:17]1)[C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=O.[CH:24]([C:26]1[CH:35]=[CH:34][C:29]([C:30]([O:32]C)=[O:31])=[CH:28][CH:27]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCCl.CO>[C:9]1([C@@H:7]2[CH2:8][C@H:6]2[NH:5][CH2:15][CH:16]2[CH2:17][N:18]([CH2:24][C:26]3[CH:35]=[CH:34][C:29]([C:30]([OH:32])=[O:31])=[CH:28][CH:27]=3)[CH2:19][CH2:20][O:21]2)[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

参加物

7

反応物 4

HCID 14798Sodium HydroxideHCID 15294Methyl 4-FormylbenzoateHCID 5049666Sodium triacetoxyborohydrideHCID 867082742,2,2-Trifluoro-N-(morpholin-2-ylmethyl)-N-((1R,2S)-2-phenylcyclopropyl)acetamide

生成物 1

HCID 665715394-((2-((((1R,2S)-2-phenylcyclopropyl)amino)methyl)morpholino)methyl)benzoic acid収率 72.5%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 887Methanol溶媒

実験手順

To a solution of 2,2,2-trifluoro-N-(morpholin-2-ylmethyl)-N-((1R,2S)-2-phenylcyclopropyl)acetamide (100 mg, 0.305 mmol) in 1,2-dichloroethane (DCE) (2 mL) were added methyl 4-formylbenzoate (60.0 mg, 0.365 mmol) and sodium triacetoxyborohydride (97 mg, 0.457 mmol), and the mixture was stirred at room temperature for 18 h. The reaction was then quenched with water (5 mL) and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated. The residue was dissolved into methanol (3.00 mL) and sodium hydroxide (6M, 0.5 mL, 3.00 mmol) was added. The mixture was stirred at room temperature for 18 h and purified using reverse-phase HPLC. The fractions containing the product were combined, treated with 1N HCl and concentrated. The residue was dried under vacuum to give 81 mg of product (HCl salt) as white solid. MS: (M+H)+=367.2. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16-1.36 (m, 1H), 1.50 (br. s., 1H), 2.93 (br. s., 2H), 3.10 (br. s., 2H), 3.35 (br. s., 2H), 4.05 (br. s., 2H), 4.36 (br. s., 2H), 7.10-7.39 (m, 5H), 7.74 (br. s., 2H) 8.01 (m, 2H).

後処理

  1. customThe reaction was then quenched with water (5 mL)
  2. extractionextracted with DCM (3×)
  3. dry with materialThe extract was dried (Na2SO4)
  4. concentrationconcentrated
  5. additionwas added
  6. stirringThe mixture was stirred at room temperature for 18 h
  7. custompurified
  8. additionThe fractions containing the product
  9. additiontreated with 1N HCl
  10. concentrationconcentrated
  11. customThe residue was dried under vacuum

出典と根拠

ORDレコード
ord-252611d798964330aaa54197a8047d5d
出典データセット
uspto-grants-2016_05
特許番号
US09346840B2

反応ノート

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