Ethyl Acetate → HCID 178448636, 화합물

HRID 1931128노트

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HRID 1931128 반응식
[CH2:1]([N:5]1[N:6]([CH3:28])[C:7]([C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:8]/[C:9]/1=[N:10]\[C:11](=[O:23])[C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:13]=1F)[CH2:2][CH2:3][CH3:4].Cl.[C:30]([NH:34][OH:35])([CH3:33])([CH3:32])[CH3:31].CC(C)([O-])C.[K+].CCOC(C)=O>C1COCC1.CCN(CC)CC.CO>[C:30]([NH:34][O:35][C:13]1[CH:14]=[CH:15][C:16]([C:18]([F:20])([F:21])[F:19])=[CH:17][C:12]=1[C:11](/[N:10]=[C:9]1/[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[N:6]([CH3:28])[C:7]([C:24]([CH3:26])([CH3:27])[CH3:25])=[CH:8]/1)=[O:23])([CH3:33])([CH3:32])[CH3:31]

참가 물질

8

반응물 4

HCID 8857Ethyl Acetate2회HCID 2777896N-tert-butylhydroxylamine hydrochlorideHCID 23665647Potassium tert-butoxide2회HCID 178448620HCID 178448620, 화합물

생성물 1

HCID 178448636HCID 178448636, 화합물수율 80%

시약·촉매·용매 3

HCID 887Methanol용매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매

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온도
40 °C

실험 절차

To a solution of Example 81C (0.45 g, 1.1 mmol) and N-(tert-butyl)hydroxylamine hydrochloride (0.28 g, 2.3 mmol) in THF (20 mL) was added potassium tert-butoxide (0.19 g, 1.7 mmol). The mixture was warmed to 40° C. and stirred for 18 hours then additional potassium tert-butoxide was added (0.40 g). The mixture was stirred for an additional 1 hour then partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×10 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated. Purification by column chromatography (SiO2, 50% hexanes/EtOAc then 100% EtOAc then 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (0.41 g, 0.88 mmol, 78% yield). 1H NMR (300 MHz, CDCl3) δ ppm 0.96 (t, J=7.3 Hz, 3H) 1.20 (s, 9H) 1.34-1.43 (m, 2H) 1.42 (s, 9H) 1.64-1.72 (m, 2H) 3.72 (s, 3H) 4.27 (dd, J=7.5 Hz, 2H) 5.75 (s, 1H) 7.01 (s, 1H) 7.46 (dd, J=8.6, 1.9 Hz, 1H) 7.67 (d, J=8.8 Hz, 1H) 8.10 (d, J=2.0 Hz, 1H); MS (DCI/NH3) m/z 469 (M+H)+; Anal. calculated for C24H35F3N4O2: Calc: C, 61.52; H, 7.53; N, 11.96. Found: C, 61.18; H, 7.26; N, 11.92.

후처리

  1. stirringThe mixture was stirred for an additional 1 hour
  2. customthen partitioned between saturated aqueous NaHCO3 (10 mL) and EtOAc (10 mL)
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc (3×10 mL)
  5. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography (SiO2, 50% hexanes/EtOAc

출처 및 근거

ORD 기록
ord-1d143255a5f149938a2b9283af38fecb
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188135B2

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