Ammonium Chloride → (5-((tert-Butyldiphenylsilyloxy)methyl)-3-chloro-4-((2R,6S)-2,6-dimethylmorpholino)-2-fluorophenyl)(pyrazin-2-yl)methanone

HRID 245395

反応式

HRID 245395 の反応式
[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([Cl:34])[C:23]([F:35])=[CH:22][CH:21]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]N1C(C)(C)CCCC1(C)C.CON(C)[C:50]([C:52]1[CH:57]=[N:56][CH:55]=[CH:54][N:53]=1)=[O:51].[NH4+].[Cl-]>C1COCC1>[Si:1]([O:18][CH2:19][C:20]1[C:25]([N:26]2[CH2:31][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]2)=[C:24]([Cl:34])[C:23]([F:35])=[C:22]([C:50]([C:52]2[CH:57]=[N:56][CH:55]=[CH:54][N:53]=2)=[O:51])[CH:21]=1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

参加物

6

反応物 4

HCID 25517Ammonium ChlorideHCID 22613131N-Methoxy-N-methylpyrazine-2-carboxamideHCID 67359669(2R,6S)-[6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-chloro-3-fluorophenyl]-2,6-dimethylmorpholine2 回HCID 178418821HCID 178418821、化合物

生成物 1

HCID 86658063(5-((tert-Butyldiphenylsilyloxy)methyl)-3-chloro-4-((2R,6S)-2,6-dimethylmorpholino)-2-fluorophenyl)(pyrazin-2-yl)methanone

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of butyllithium, 2.5M in hexanes (1.718 mL, 4.30 mmol) was added dropwise to a solution of 2,2,6,6-tetramethylpiperidine (0.802 mL, 4.73 mmol) in 15 ml THF at −78° C. The flask was removed from the −78° C. bath, and stirred at ca 0° C. for 10 minutes, then recooled to −78° C. to give a pale yellow solution of LiTMP. A solution of (2R,6S)-4-[6-({[tert-butyl(diphenyl)silyl]oxy}methyl)-2-chloro-3-fluorophenyl]-2,6-dimethylmorpholine (Intermediate 42, 1.1 g, 2.15 mmol) 20 ml THF was cannulated into the LiTMP solution to give a yellow solution which was stirred at −78 for about 1 hour; then N-methoxy-N-methylpyrazine-2-carboxamide (1.077 g, 6.44 mmol) was added. The mixture was stirred at −78° C. After 5 hours the reaction was worked up by adding saturated NH4Cl to the −78° C. solution and extracting with EtOAc (3×). After drying over MgSO4, concentration of the mixture gave material that was purified on SiO2 using 0-10% acetone/hexanes to recover 891 mg (67%) of the title compound as a yellow oil.

後処理

  1. customto give a yellow solution which
  2. stirringThe mixture was stirred at −78° C
  3. waitAfter 5 hours the reaction was worked up
  4. extractionextracting with EtOAc (3×)
  5. dry with materialAfter drying over MgSO4, concentration of the mixture
  6. customgave material that
  7. customwas purified on SiO2 using 0-10% acetone/hexanes
  8. customto recover 891 mg (67%) of the title compound as a yellow oil

出典と根拠

ORDレコード
ord-8478dd129ea648f29ac85641a746e630
出典データセット
uspto-grants-2014_02
特許番号
US08658641B2

関連ノート

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