Triethylamine → 3-(3-Cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester

HRID 346891노트

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HRID 346891 반응식
[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH:5]([NH2:21])[C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:13]([F:15])[F:14])=[C:8]([O:16][CH2:17][CH:18]2[CH2:20][CH2:19]2)[CH:7]=1.C(N(CC)CC)C.C([O:32][C:33](=O)[C:34]1[C:39]([N+:40]([O-:42])=[O:41])=[CH:38][CH:37]=[CH:36][C:35]=1[CH2:43]Br)C>CN(C=O)C>[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH:5]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH:13]([F:14])[F:15])=[C:8]([O:16][CH2:17][CH:18]2[CH2:19][CH2:20]2)[CH:7]=1)[N:21]1[CH2:43][C:35]2[C:34](=[C:39]([N+:40]([O-:42])=[O:41])[CH:38]=[CH:37][CH:36]=2)[C:33]1=[O:32]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 13000593Ethyl 2-(bromomethyl)-6-nitrobenzoateHCID 588000783-Amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid methyl ester

생성물 1

HCID 103902253-(3-Cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester수율 77%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

To a solution of 3-amino-3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-propionic acid methyl ester (490 mg, 1.5 mmol) and triethyl amine (0.43 ml, 3.1 mmol) in DMF (10 ml) was added 2-bromomethyl-6-nitro-benzoic acid ethyl ester (460 mg, 1.6 mmol). The mixture was heated at 90° C. under nitrogen atmosphere overnight. The solvent was removed in vacuo. The resulted oil was extracted with ethyl acetate (50 ml) and 1N HCl (50ml). The organic layer was washed with water (30 ml), brine (30 ml) and dried over magnesium sulfate. The solvent was removed in vacuo and the resulted oil was purified by silica gel chromatography (hexane: ethyl acetate=2:1) to give 3-(3-cyclopropylmethoxy-4-difluoromethoxy-phenyl)-3-(7-nitro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester as a yellowish solid (550 mg, 75%). 1HNMR (CDCl3): δ 0.31–0.37 (m, 2H), 0.59–0.67 (m, 2H), 1.22–1.28 (m, 1H), 3.09 (dd, J=7, 15 Hz, 1H), 3.28 (dd, J=9, 15 Hz, 1H), 3.65 (s, 3H), 3.79–3.91 (m, 2H), 4.18 (d, J=17 Hz, 1H), 4.46 (d, J=17 Hz, 1H), 5.83 (dd, J=7, 9 Hz, 1H), 6.61 (t, JH-F=75 Hz, 1H), 7.04–7.05 (m, 3H), 7.58–7.76 (m, 3H).

후처리

  1. customThe solvent was removed in vacuo
  2. extractionThe resulted oil was extracted with ethyl acetate (50 ml) and 1N HCl (50ml)
  3. washThe organic layer was washed with water (30 ml), brine (30 ml)
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed in vacuo
  6. customthe resulted oil was purified by silica gel chromatography (hexane: ethyl acetate=2:1)

출처 및 근거

ORD 기록
ord-434b7fd8ea54496891d6170eb5619acc
출처 데이터셋
uspto-grants-2007_02
특허 번호
US07173058B2

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