Hydrochloric Acid → HCID 59511925、化合物

HRID 1157655ノート

反応式

HRID 1157655 の反応式
Br[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1.C([Li])CCC.[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C:21]1=[O:25])=[O:19])([CH3:16])([CH3:15])[CH3:14].Cl.C(OCC)C>O1CCCC1.O.ClCCl>[C:13]([O:17][C:18](=[O:19])[NH:20][CH2:24][CH2:23][CH2:22][C:21](=[O:25])[C:2]1[CH:3]=[N:4][CH:5]=[N:6][CH:7]=1)([CH3:16])([CH3:14])[CH3:15]

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 783445-BromopyrimidineHCID 3790001-Pyrrolidinecarboxylic acid, 2-oxo-, 1,1-dimethylethyl esterHCID 178418339Butyllithium

生成物 1

HCID 59511925HCID 59511925、化合物収率 94.9%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

Cool a solution of 5-bromopyrimidine (7.63 g, 48.0 mmol) in tetrahydrofuran (375 mL) to −100° C., and add slowly n-butyllithium (2.5 M in hexanes, 17.8 mL, 44.5 mmol), keeping the temperature below −90° C. Stir the reaction for 30 min at −100° C. Cool a solution of 1-(tert-butoxycarbonyl)-2-pyrrolidinone (8.08 g, 43.6 mmol) in tetrahydrofuran (100 mL) to −78° C. and add to the reaction mixture with a cannula. Stir the reaction at −100° C. for 30 min, then add a 2 M solution of hydrogen chloride in diethyl ether (25 mL, 50 mmol). Allow the reaction to warm to room temperature and add dichloromethane (500 mL) and water (500 mL). Separate the layers and extract the aqueous layer with dichloromethane (2×250 mL). Combine the organic portions and wash with brine (400 mL), dry over magnesium sulfate, filter, and evaporate under reduced pressure to afford a crude mixture (10.98 g). Purify by flash chromatography (two stacked 120 g RediSep silica gel columns, 0:100 to 30:70 gradient of [90:10:1 dichloromethane:methanol:concentrated ammonium hydroxide]:dichloromethane) to provide an impure mixture containing the product (5.35 g, ˜35%) which is used without further purification. MS (APCI+): 148 [C13H19N3O3—C5H8O2—H2O+H]+; 1H NMR (300 MHz, CDCl3): δ 9.36 (s, 1H), 9.22 (s, 2H), 4.63 (br s, 1H), 3.19-3.29 (m, 2H), 3.04 (t, J=7.0 Hz, 2H), 1.97 (quintet, J=6.8 Hz, 2H), 1.41 (s, 9H).

後処理

  1. customthe temperature below −90° C
  2. customthe reaction for 30 min at −100° C
  3. additionadd to the reaction mixture with a cannula
  4. stirringStir
  5. customthe reaction at −100° C. for 30 min
  6. customthe reaction
  7. customSeparate the layers
  8. extractionextract the aqueous layer with dichloromethane (2×250 mL)
  9. washCombine the organic portions and wash with brine (400 mL)
  10. dry with materialdry over magnesium sulfate
  11. filtrationfilter
  12. customevaporate under reduced pressure

出典と根拠

ORDレコード
ord-9700d46713e44daa922c8f0e54200f6d
出典データセット
uspto-grants-2010_10
特許番号
US07807691B2

反応ノート

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