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Ethylamine → 5-((tert-butyldiphenylsilyloxy)methyl)-6-((2R,6S)-2,6-dimethylmorpholino)-N-ethyl-7-fluorobenzo[d]isoxazole-3-carboxamide

HRID 245457
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HRID 245457 반응식
C[Al](C)C.[CH2:5]([NH2:7])[CH3:6].[Si:8]([O:25][CH2:26][C:27]1[C:28]([N:42]2[CH2:47][C@H:46]([CH3:48])[O:45][C@H:44]([CH3:49])[CH2:43]2)=[C:29]([F:41])[C:30]2[O:34][N:33]=[C:32]([C:35](OCC)=[O:36])[C:31]=2[CH:40]=1)([C:21]([CH3:24])([CH3:23])[CH3:22])([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C1(C)C=CC=CC=1>[Si:8]([O:25][CH2:26][C:27]1[C:28]([N:42]2[CH2:43][C@H:44]([CH3:49])[O:45][C@H:46]([CH3:48])[CH2:47]2)=[C:29]([F:41])[C:30]2[O:34][N:33]=[C:32]([C:35]([NH:7][CH2:5][CH3:6])=[O:36])[C:31]=2[CH:40]=1)([C:21]([CH3:22])([CH3:24])[CH3:23])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
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참가 물질

5

반응물 3

HCID 6341EthylamineHCID 16682925TrimethylaluminumHCID 67357675ethyl 5-((tert-butyldiphenylsilyloxy)methyl)-6-((2R,6S)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-3-carboxylate2회

생성물 1

HCID 673575425-((tert-butyldiphenylsilyloxy)methyl)-6-((2R,6S)-2,6-dimethylmorpholino)-N-ethyl-7-fluorobenzo[d]isoxazole-3-carboxamide

시약·촉매·용매 1

HCID 1140
Toluene
용매
2회

실험 절차

Under a nitrogen atmosphere, trimethylaluminum (2M in toluene, 1206 μl, 2.41 mmol) was slowly added (gas evolution) to an ice cooled solution of ethylamine (2M in THF) (1206 μl, 2.41 mmol) in 7 ml of toluene. The reaction was allowed to warm to room temperature and stirred for 2 hours. Ethyl 5-((tert-butyldiphenylsilyloxy)methyl)-6-((2R,6S)-2,6-dimethylmorpholino)-7-fluorobenzo[d]isoxazole-3-carboxylate, (Intermediate 204, 190 mg, 0.32 mmol) was added as a solution in toluene (3 ml). The reaction was stirred at 45° C. for 18 hours. The reaction was quenched drop wise (vigorous gas evolution) with 2 ml of 1N HCl. The crude reaction was filtered to remove solids, diluted with water and extracted twice with ethyl acetate. The organic layers were combined, washed twice with brine, dried over MgSO4 and concentrated to give an oil. The oil was purified by silica gel column chromatorgraphy using a gradient of hexanes to ethyl acetate. Fractions were combined and concentrated to give the title compound. (170 mg, 0.288 mmol, 90%).

후처리

  1. stirringThe reaction was stirred at 45° C. for 18 hours
  2. customThe reaction was quenched drop wise (vigorous gas evolution) with 2 ml of 1N HCl
  3. customThe crude reaction
  4. filtrationwas filtered
  5. customto remove solids
  6. additiondiluted with water
  7. extractionextracted twice with ethyl acetate
  8. washwashed twice with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. customto give an oil
  12. customThe oil was purified by silica gel column chromatorgraphy
  13. concentrationconcentrated

출처 및 근거

ORD 기록
ord-40dbd40fe20c4ad6b7f12c3d7cc0f27d
출처 데이터셋
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08658641B2

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