Hydrochloric Acid → N,N-Diethyl-2-formyl-6-methoxybenzamide

HRID 1968766노트

반응식

HRID 1968766 반응식
C([Li])(CC)C.CN(C)CCN(C)C.[CH2:14]([N:16]([CH2:27][CH3:28])[C:17](=[O:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[O:24][CH3:25])[CH3:15].CN(C)[CH:31]=[O:32].Cl>C1COCC1>[CH2:27]([N:16]([CH2:14][CH3:15])[C:17](=[O:26])[C:18]1[C:19]([O:24][CH3:25])=[CH:20][CH:21]=[CH:22][C:23]=1[CH:31]=[O:32])[CH3:28]

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 346975N,N-diethyl-2-methoxybenzamideHCID 178418400CID 53628100

생성물 1

HCID 12460617N,N-Diethyl-2-formyl-6-methoxybenzamide수율 105.5%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

Sec-butyl lithium (99.6 ml, 1.3 M in cyclohexane, 129.45 mmol, 1.3 equiv) was added dropwise at −78° C. to a solution of N,N,N′,N′-tetramethyl-ethane-1,2-diamine (15.04 g, 129.45 mmol, 1.3 equiv) in anhydrous THF (400 ml) under an atmosphere of argon. After 30 minutes at −78° C., a solution of N,N-diethyl-2-methoxy-benzamide (20.64 g, 99.58 mmol) in THF (100 ml) was added dropwise over 50 minutes. After 2 hours at −78° C., N,N-dimethylformamide (8.74 g, 119.49 mmol, 1.2 equiv) was added dropwise. 30 minutes after complete addition, TLC analysis indicated complete conversion. 6N aqueous HCl (90 ml) was carefully added at 0° C. After phase separation, the aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine (2×100 ml), dried over Na2SO4, filtered and concentrated in vacuo to yield the title compound (24.71 g, quant.) in adequate purity for direct use in the next transformation. 1H NMR (400 MHz, CDCl3): δ=9.99 (s, 1H), 7.52 (dd, J=6.6/1.0 Hz, 1H), 7.46 (t, 7.6 Hz, 1H), 7.15 (dd, J=8.3/1.2 Hz, 1H), 3.86 (s, 3H), 3.78-3.68 (m, 1H), 3.58-3.49 (m, 1H), 3.10 (q, J=7.1 Hz, 2H), 1.29 (t, J=7.1 Hz, 3H), 1.01 (t, J=7.3 Hz, 3H). MS (ES+): 236 (M+H)+.

후처리

  1. waitAfter 2 hours at −78° C.
  2. addition30 minutes after complete addition, TLC analysis
  3. customAfter phase separation
  4. extractionthe aqueous phase was extracted with EtOAc
  5. washThe combined organic layers were washed with brine (2×100 ml)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-f4b9d95fb24d45eda953c972243c0f5c
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426440B2

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