Hexachloroethane → (R)-3-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 630849ノート

反応式

HRID 630849 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([C:13]([NH:15][NH:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=2)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC.ClC(Cl)(Cl)C(Cl)(Cl)Cl.CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>C1COCC1.C(Cl)Cl.CO.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([C:13]2[N:18]3[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]3=[N:16][N:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

10

反応物 5

HCID 6214HexachloroethaneHCID 8471Triethylamine2 回HCID 11776TriphenylphosphineHCID 90495Di-tert-butyl dicarbonateHCID 89624955(R)-3-[N'-(5-Fluoro-pyridin-2-yl)-hydrazinocarbonyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 86687137(R)-3-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester収率 73%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a brown solution Intermediate 90a (1.37 g, 4.22 mmol), Ph3P (2.22 g, 8.45 mmol) and Et3N (2.35 mL, 16.9 mmol) in THF (25 mL) at 0° C. was added hexachloroethane (2.00 g, 8.45 mmol) in 3 portions at 1 min intervals. The solution was stirred at 0° C. for 30 min and at RT for 3.5 h. The suspension was filtered and the filter-cake washed with THF (10 mL). The combined organics were applied to an SCX-2 cartridge (50 g), then washed with DCM-MeOH (1:1, 50 mL) and MeOH (50 mL). The product was eluted with 2M NH3 in MeOH (75 mL); concentration in vacuo gave a brown oil that solidified on standing. The solid was dissolved in DCM (10 mL) then Et3N (0.580 mL, 4.16 mmol) and BOC anhydride (454 mg, 2.08 mmol) added sequentially. The solution was stirred at RT for 45 min, then water (10 mL) was added and the aqueous extracted with DCM (5 mL). The combined organics were passed through a hydrophobic frit and concentrated in vacuo to leave a brown gum. FCC, using 2.5-3% MeOH in DCM, gave the title compound as a pale brown solid (933 mg, 73%). LCMS (Method 3): Rt 2.94 min, m/z 207 [MH+-C5H9O2].

後処理

  1. filtrationThe suspension was filtered
  2. washthe filter-cake washed with THF (10 mL)
  3. washwashed with DCM-MeOH (1:1, 50 mL) and MeOH (50 mL)
  4. washThe product was eluted with 2M NH3 in MeOH (75 mL)
  5. concentrationconcentration in vacuo
  6. customgave a brown oil that
  7. stirringThe solution was stirred at RT for 45 min
  8. extractionthe aqueous extracted with DCM (5 mL)
  9. concentrationconcentrated in vacuo
  10. customto leave a brown gum

出典と根拠

ORDレコード
ord-a51f4d58331c4631942a0c25ca5bb568
出典データセット
uspto-grants-2016_04
特許番号
US09315503B2

反応ノート

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