Diisopropylamine → HCID 67358619, 화합물

HRID 245429

반응식

HRID 245429 반응식
C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[Li+].CC([N-]C(C)C)C.[Si:27]([O:44][CH2:45][C:46]1[C:51]([N:52]2[CH2:57][C@H:56]([CH3:58])[O:55][C@H:54]([CH3:59])[CH2:53]2)=[C:50]([Cl:60])[C:49]([F:61])=[CH:48][N:47]=1)([C:40]([CH3:43])([CH3:42])[CH3:41])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CON(C)[C:65](=[O:72])[C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][N:67]=1>C1COCC1>[Si:27]([O:44][CH2:45][C:46]1[N:47]=[C:48]([C:65]([C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][N:67]=2)=[O:72])[C:49]([F:61])=[C:50]([Cl:60])[C:51]=1[N:52]1[CH2:57][C@H:56]([CH3:58])[O:55][C@H:54]([CH3:59])[CH2:53]1)([C:40]([CH3:43])([CH3:41])[CH3:42])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

참가 물질

8

반응물 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 2724682Lithium diisopropylamideHCID 11829796N-Methoxy-N-methylpicolinamideHCID 67319975(2R,6S)-4-(2-((tert-Butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine2회HCID 178418339Butyllithium

생성물 1

HCID 67358619HCID 67358619, 화합물수율 67.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
0 °C

실험 절차

Diisopropylamine (0.925 mL, 6.55 mmol) was added dropwise to a stirring solution of 2.5M n-butyllithium in hexane (2.495 mL, 6.24 mmol) in THF (10 mL) at −78° C. Allowed solution to warm to 0° C. for 10 minutes then cooled again to −78° C. Cannulated the prepared LDA at −78° C. into (2R,6S)-4-(2-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine (Intermediate 45, 1.6 g, 3.12 mmol) in THF (10 mL) at −78° C. Allowed the dark solution to stir for 20 minutes and then cannulated into a stirring solution of N-methoxy-N-methylpicolinamide (1.05 g, 6.24 mmol) in THF (10 mL) at −78° C. Allowed the solution to warm to −50° C. and then quenched with saturated ammonium chloride solution. Extracted mixture with ethyl acetate and washed resulting organics with brine. Dried organics over sodium sulfate, filtered, and evacuated filtrate under vacuum to give crude yellow oil. The crude oil was purified on silica using 10-30% acetone in n-hexane as eluant to give 1.3 g (67%) of the title compound as oil.

후처리

  1. temperaturethen cooled again to −78° C
  2. customat −78° C.
  3. customat −78° C
  4. temperatureAllowed the solution to warm to −50° C.
  5. customquenched with saturated ammonium chloride solution
  6. extractionExtracted mixture with ethyl acetate
  7. washwashed
  8. customresulting organics with brine
  9. filtrationDried organics over sodium sulfate, filtered
  10. customevacuated filtrate under vacuum
  11. customto give crude yellow oil
  12. customThe crude oil was purified on silica using 10-30% acetone in n-hexane as eluant

출처 및 근거

ORD 기록
ord-b080f6c617d74125a6d08c595459593d
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658641B2

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