Sulfuric Acid → 2-(4-Hydroxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester

HRID 1183609노트

반응식

HRID 1183609 반응식
S(=O)(=O)(O)O.[CH2:6]([O:8][C:9](=[O:26])[CH:10]([C:15]1[CH:20]=[CH:19][C:18](N)=[C:17]([C:22]([F:25])([F:24])[F:23])[CH:16]=1)[CH2:11][CH:12]([CH3:14])[CH3:13])[CH3:7].[N:27]([O-:29])=[O:28].[Na+].NC(N)=[O:33]>O.C(OCC)C>[CH2:6]([O:8][C:9](=[O:26])[CH:10]([C:15]1[CH:16]=[C:17]([C:22]([F:25])([F:24])[F:23])[C:18]([OH:33])=[C:19]([N+:27]([O-:29])=[O:28])[CH:20]=1)[CH2:11][CH:12]([CH3:14])[CH3:13])[CH3:7]

참가 물질

7

반응물 4

HCID 1118Sulfuric AcidHCID 1176UreaHCID 23668193Sodium Nitrite2회HCID 579955332-(4-Amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester

생성물 1

HCID 579955452-(4-Hydroxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester수율 31%

시약·촉매·용매 2

HCID 962Water용매3회HCID 3283Diethyl Ether용매

반응 조건

온도
0 °C

실험 절차

To sulfuric acid (95-98%, 20.0 mL) was added 2-(4-amino-3-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (6.06 g, 20.0 mmol). The mixture was cooled to 0° C. and water (30.0 mL) was added dropwise. A solution of NaNO2 (1.66 g, 24.0 mmol) in water (12 mL) was added dropwise and the mixture was stirred for additional 20 min. A few crystals of urea were added to decompose any excess NaNO2. A solution of cupric nitrate (466 g, 2.00 mol) in water (880 mL) was added, followed by addition of Cu2O (2.86 g, 20.0 mmol). The mixture was stirred for 5 min and diethyl ether (1 L) was added. The organic extract was washed with brine (500 mL), dried over Na2SO4, and concentrated under reduced pressure. The residue was purified by silica-gel flash chromatography eluting with heptane/ethyl acetate (20:1) to give 2-(4-hydroxy-3-nitro-5-trifluoromethyl-phenyl)-4-methyl-pentanoic acid ethyl ester (2.20 g, 31%) as a yellow oil: HRMS (DIP-CI-MS): calcd for C15H19NO5F3 (M+H)+: 350.1215, found 350.1240; 1H NMR (300 MHz, CDCl3): δ 11.13 (s, 1H), 8.29 (s, 1H), 7.90 (s, 1H), 4.15 (m, 2H), 3.69 (t, 1H, J=7.8 Hz), 2.00 (m, 1H), 1.62 (m, 1H), 1.47 (m, 1H), 1.25 (t, 3H, J=7.2 Hz), 0.94 (d, 3H, J=6.3 Hz), 0.93 (d, 3H, J=6.6 Hz); 13C NMR (75 MHz, CDCl3): δ 172.75, 152.45, 134.67 (q, J=5 Hz), 134.29, 131.40, 127.90, 122.35, (q, J=271 Hz), 121.42 (q, J=32 Hz), 61.51, 48.76, 42.76, 26.23, 22.60, 22.42, 14.32.

후처리

  1. stirringThe mixture was stirred for 5 min
  2. extractionThe organic extract
  3. washwas washed with brine (500 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica-gel flash chromatography
  7. washeluting with heptane/ethyl acetate (20:1)

출처 및 근거

ORD 기록
ord-8bfcd5e933be47168d670fb44654234e
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08664249B2

반응 노트

불러오는 중…