tert-Butanol → HCID 57758674、化合物

HRID 17628ノート

反応式

HRID 17628 の反応式
C(Cl)(=O)C(Cl)=O.[O:7]=[C:8]1[N:12]([C@@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[CH2:11][CH:10]([C:21]([OH:23])=[O:22])[CH2:9]1.[C:24](O)([CH3:27])([CH3:26])[CH3:25].C(N(CC)CC)C>O.CN(C)C=O.ClCCl>[O:7]=[C:8]1[N:12]([C@@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[CH2:11][CH:10]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:9]1

参加物

8

反応物 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 134225555-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid

生成物 1

HCID 57758674HCID 57758674、化合物

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

With cooling with ice, oxalyl chloride (15.7 ml, 0.18 mol) was dropwise added to a dichloromethane (200 ml) solution of 5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid (35 g, 0.15 mol) synthesized according to the method described in J. Med. Chem., 30, 1711-1715 (1987), then a catalytic amount of N,N-dimethylformamide was added, followed by stirring as such for 1 hour, then warming up to room temperature and further stirring for 1 hour. The reaction liquid was dried to solidness under reduced pressure (toluene azeotropy three times). This was dissolved in dichloromethane (100 ml), and the solution was dropwise added to a dichloromethane (150 ml) solution containing tert-butanol (43 ml, 0.45 mol) with cooling with ice. Triethylamine (31.4 ml, 0.225 mol) was further dropwise added at the same temperature, followed by stirring at room temperature for 16 hours. Water was added to the reaction liquid, and the dichloromethane layer was collected, and this was washed with water and saturated brine. After drying over anhydrous sodium sulfate and concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (eluent, n-hexane:ethyl acetate=3:1→1:1→1:2→1:3, v/v) to obtain the entitled compound (including mixture of optical isomers) (34.227 g in total, 79%). This was used in the next, reaction as such.

後処理

  1. customsynthesized
  2. stirringfurther stirring for 1 hour
  3. customThe reaction liquid
  4. dry with materialwas dried to solidness under reduced pressure (toluene azeotropy three times)
  5. dissolutionThis was dissolved in dichloromethane (100 ml)
  6. additionthe solution was dropwise added to a dichloromethane (150 ml) solution
  7. temperaturewith cooling with ice
  8. stirringby stirring at room temperature for 16 hours
  9. customthe dichloromethane layer was collected
  10. washthis was washed with water and saturated brine
  11. dry with materialAfter drying over anhydrous sodium sulfate and concentration under reduced pressure
  12. customthe resulting residue was purified by silica gel column chromatography (eluent, n-hexane
  13. customethyl acetate=3:1→1:1→1:2→1:3, v/v) to obtain
  14. additionthe entitled compound (including mixture of optical isomers) (34.227 g in total, 79%)
  15. customreaction as such

出典と根拠

ORDレコード
ord-85c1a58c6c194b40ae1336e2723a19e8
出典データセット
uspto-grants-2010_06
特許番号
US07737166B2

反応ノート

読み込み中…