Methanol → Trifluoroacetic acid

HRID 1506370ノート

反応式

HRID 1506370 の反応式
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]3[C:16]4[C:21]([CH2:22][CH2:23][C:12]=23)=[CH:20][C:19]([CH:24]=O)=[CH:18][CH:17]=4)=[CH:7][C:6]=1[C:26]([F:29])([F:28])[F:27])[CH:2]([CH3:4])[CH3:3].[NH:30]1[CH2:33][CH:32]([C:34]([OH:36])=[O:35])[CH2:31]1.C([BH3-])#N.[Na+].[CH3:41][OH:42]>ClC(Cl)C.CC(O)=O>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][N:14]=[C:13]3[C:16]4[C:21]([CH2:22][CH2:23][C:12]=23)=[CH:20][C:19]([CH2:24][N:30]2[CH2:33][CH:32]([C:34]([OH:36])=[O:35])[CH2:31]2)=[CH:18][CH:17]=4)=[CH:7][C:6]=1[C:26]([F:29])([F:28])[F:27])[CH:2]([CH3:4])[CH3:3].[C:41]([OH:35])([C:26]([F:29])([F:28])[F:27])=[O:42]

参加物

8

反応物 4

HCID 887MethanolHCID 931923-azetidinecarboxylic AcidHCID 5003444Sodium cyanoborohydrideHCID 866698863-(4-Isobutyl-3-(trifluoromethyl)phenyl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde

生成物 2

HCID 6422Trifluoroacetic acid収率 32.5%HCID 671720391-((3-(4-Isobutyl-3-(trifluoromethyl)phenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)azetidine-3-carboxylic acid

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 63651,1-Dichloroethane溶媒

反応条件

温度
80 °C

実験手順

To 3-(4-isobutyl-3-(trifluoromethyl)phenyl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde (Preparation 23D, 0.3 g, 0.751 mmol) in dichloroethane (2 mL) and methanol (2 mL) was added azetidine-3-carboxylic acid (0.091 g, 0.901 mmol) followed by 8 drops of AcOH. The reaction mixture was heated at 80° C. for 1 h. The reaction mixture was cooled to room temperature and sodium cyanoborohydride was added in one lot. The contents were stirred at room temperature for 30 min., concentrated, dissolved in acetonitrile (1.5 mL) and subjected to prep. HPLC purification PHENOMENEX® Luna Axia 30×100 mm; 10 min. gradient; solvent A=10% MeOH, 90% H2O, 0.1% TFA, solvent B=90% MeOH, 10% H2O, 0.1% TFA). Fractions corresponding to the product were collected and concentrated. The oily residue was freeze dried to yield 1-((3-(4-isobutyl-3-(trifluoromethyl)phenyl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)methyl)azetidine-3-carboxylic acid, TFA (0.146 g, 0.244 mmol, 32.5% yield) as a tan solid. The compound had an HPLC retention time=3.55 min. (condition C); LC/MS M+1=485.4. 1H NMR (500 MHz, MeOD) δ ppm 7.83-7.94 (m, 3H) 7.50 (d, J=8.32 Hz, 1H) 7.38 (s, 1H) 7.34 (dd, J=8.05, 1.66 Hz, 1H) 4.33 (s, 2H) 4.18-4.28 (m, 3H) 3.58 (qd, J=8.37, 8.18 Hz, 1H) 3.15 (1H, hidden under CD3OD peak) 2.96-3.01 (m, 4H) 2.62 (d, J=6.94 Hz, 2H) 1.85-1.94 (m, 1H) 0.84 (d, J=6.66 Hz, 6H).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. dissolutiondissolved in acetonitrile (1.5 mL)
  4. customHPLC purification PHENOMENEX® Luna Axia 30×100 mm
  5. custom10 min.
  6. customFractions corresponding to the product were collected
  7. concentrationconcentrated
  8. customdried

出典と根拠

ORDレコード
ord-bfe8de15c8b6402da58736010394daea
出典データセット
uspto-grants-2015_12
特許番号
US09216972B2

反応ノート

読み込み中…