Ammonium Chloride → methyl (E)-6-amino-5-(4-(phenylmethoxy)but-1-enyl)-4-(4-fluorophenyl)-2-(1-methylethyl)nicotinate

HRID 29085노트

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HRID 29085 반응식
[Br-].[CH2:2]([O:9][CH2:10][CH2:11][CH2:12][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[NH2:42][C:43]1[N:48]=[C:47]([CH:49]([CH3:51])[CH3:50])[C:46]([C:52]([O:54][CH3:55])=[O:53])=[C:45]([C:56]2[CH:61]=[CH:60][C:59]([F:62])=[CH:58][CH:57]=2)[C:44]=1[CH:63]=O.[NH4+].[Cl-]>O1CCCC1.C(OCC)(=O)C>[NH2:42][C:43]1[C:44](/[CH:63]=[CH:12]/[CH2:11][CH2:10][O:9][CH2:2][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)=[C:45]([C:56]2[CH:57]=[CH:58][C:59]([F:62])=[CH:60][CH:61]=2)[C:46]([C:52]([O:54][CH3:55])=[O:53])=[C:47]([CH:49]([CH3:51])[CH3:50])[N:48]=1

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 10929077(3-Benzyloxypropyl)triphenylphosphonium bromideHCID 11438468HCID 11438468, 화합물

생성물 1

HCID 86599979methyl (E)-6-amino-5-(4-(phenylmethoxy)but-1-enyl)-4-(4-fluorophenyl)-2-(1-methylethyl)nicotinate수율 82%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

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온도
-78 °C

실험 절차

To a suspension of (3-benzyloxypropyl)triphenyl-phosphonium bromide (8.55 g, 17.4 mmol) in tetrahydrofuran (15 mL) was added dropwise sodium bis(trimethylsilyl)amide (34.8 mL, 1.0 M in tetrahydrofuran) under nitrogen at −78° C. The reaction was stirred at −78° C. for 30 min, allowed to warm to room temperature and stirred for another 30 min. The mixture was then cooled to −78° C. and a solution of methyl 6-amino-4-(4-fluorophenyl)-5-formyl-2-(1-methylethyl)-3-pyridinecarboxylate (5.0 g, 15.8 mmol) in tetrahydrofuran (10 mL) was added dropwise over 45 min. The resulting mixture was stirred at −78° C. for 30 min, allowed to warm to room temperature and stirred for 2 h. The resulting mixture was then poured into a mixture of ice, ethyl acetate, saturated aqueous NH4Cl and was extracted with ethyl acetate. The combined organic layers were washed with brine and evaporated. The residue was equally divided and portion was purified by a silica gel chromatography (120 g column), using 0% to 45% of ethyl acetate in hexanes. The collected fractions were concentrated to provide methyl (E)-6-amino-5-(4-(phenylmethoxy)but-1-enyl)-4-(4-fluorophenyl)-2-(1-methylethyl)nicotinate as a light orange oil (5.79 g, 82%): LCMS (ESI, pos. ion spectrum) m/z 449 (M+H); HPLC (method 3) tR=3.2 min.

후처리

  1. temperatureto warm to room temperature
  2. stirringstirred for another 30 min
  3. temperatureThe mixture was then cooled to −78° C.
  4. stirringThe resulting mixture was stirred at −78° C. for 30 min
  5. temperatureto warm to room temperature
  6. stirringstirred for 2 h
  7. extractionwas extracted with ethyl acetate
  8. washThe combined organic layers were washed with brine
  9. customevaporated
  10. customportion was purified by a silica gel chromatography (120 g column)
  11. concentrationThe collected fractions were concentrated

출처 및 근거

ORD 기록
ord-a186941fd03a41509e15ae7a8208dfeb
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07420059B2

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