Methane → Tert-butyl N-tert-butoxycarbonyl-N-[5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-yl]carbamate

HRID 81380ノート

反応式

HRID 81380 の反応式
BrC1N=C(C#C[Si](C)(C)C)C(N)=NC=1.[CH3:15][C:16]1[CH:17]=CC(S(O)(=O)=O)=C[CH:21]=1.[Br:26][C:27]1[N:28]=[C:29]([C:44]#[C:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:30]([N:33]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C:34](=[O:36])[O-:35])=[N:31][CH:32]=1.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C.C>CCOC(C)=O.CN(C1C=CN=CC=1)C>[C:40]([O:39][C:37]([N:33]([C:30]1[C:29]([C:44]#[C:45][Si:46]([CH3:47])([CH3:49])[CH3:48])=[N:28][C:27]([Br:26])=[CH:32][N:31]=1)[C:34](=[O:35])[O:36][C:16]([CH3:17])([CH3:21])[CH3:15])=[O:38])([CH3:42])([CH3:43])[CH3:41]

参加物

8

反応物 5

HCID 297MethaneHCID 6101p-Toluenesulfonic acidHCID 90495Di-tert-butyl dicarbonateHCID 533931895-Bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amineHCID 86680731N-[5-bromo-3-(2-trimethylsilylethynyl)pyrazin-2-yl]-N-tertbutoxycarbonyl-carbamate

生成物 1

HCID 58070279Tert-butyl N-tert-butoxycarbonyl-N-[5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-yl]carbamate

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 8857Ethyl Acetate溶媒2 回

実験手順

A solution of 5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-amine (Compound C-2) PTSA salt 3 (2350 g, 5.31 mol) in EtOAc (11.5 L) is stirred with a 20% w/w aq. solution of KHCO3 (4.5 kg, 1.5 eq.) for at least 30 min. The layers are separated and the organic layer is concentrated then dissolved in EtOAc (7 L) and added to a reactor. DMAP (19.5 g, 0.16 mol) is added followed a solution of Boc2O (2436 g, 11.16 mol) in EtOAc (3 L) is added lowly. The reaction is stirred for at least 30 min to ensure complete reaction then activated charcoal (Darco G-60, 720 g) and Celite (720 g) are added and stirred for at least 2 h. The mixture is filtered washing the solid pad with EtOAc (2×1.8 L). The filtrate is concentrated to afford tert-butyl N-tert-butoxycarbonyl-N-[5-bromo-3-((trimethylsilyl)ethynyl)pyrazin-2-yl]carbamate (Compound C-3) that is used directly in the next step.

後処理

  1. customThe layers are separated
  2. concentrationthe organic layer is concentrated
  3. dissolutionthen dissolved in EtOAc (7 L)
  4. additionadded to a reactor
  5. additionis added lowly
  6. customreaction
  7. stirringstirred for at least 2 h
  8. filtrationThe mixture is filtered
  9. washwashing the solid pad with EtOAc (2×1.8 L)
  10. concentrationThe filtrate is concentrated

出典と根拠

ORDレコード
ord-8e13d50c4b5f459cbacffa6ab52b8660
出典データセット
uspto-grants-2014_09
特許番号
US08846686B2

反応ノート

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