Triethylamine → HCID 67145028、化合物

HRID 1695320ノート

反応式

HRID 1695320 の反応式
[Br:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[C:16]([O:17][CH3:18])=[CH:15][C:11]([C:12]([OH:14])=O)=[C:10]([N+:19]([O-:21])=[O:20])[CH:9]=1.C(Cl)(=O)C(Cl)=O.[CH3:28][O:29][C:30](=[O:37])[C@@H:31]1[CH2:35][C:34](=[CH2:36])[CH2:33][NH:32]1.CCN(CC)CC>CN(C=O)C.C1COCC1.O>[CH3:28][O:29][C:30](=[O:37])[C@@H:31]1[CH2:35][C:34](=[CH2:36])[CH2:33][N:32]1[C:12](=[O:14])[C:11]1[CH:15]=[C:16]([O:17][CH3:18])[C:8]([O:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][Br:1])=[CH:9][C:10]=1[N+:19]([O-:21])=[O:20]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11002937HCID 11002937、化合物HCID 450899474-Methylene-L-proline methyl ester

生成物 1

HCID 67145028HCID 67145028、化合物

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide触媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A catalytic amount of DMF (2 drops) was added to a solution of 4-(5-bromopentyloxy)-5-methoxy-2-nitro-benzoic acid 17 (270 mg, 0.74 mmol) and oxalyl chloride (80 μL, 0.89 mmol) in anhydrous THF (7.5 mL) and the resulting mixture was stirred at rt for an overnight. Excess THF and oxalyl chloride were removed with rotavapor. The acetyl chloride was resuspended in fresh THF (6 mL) and was added dropwise to a solution of 4-methylene-L-proline methyl ester 5 (228 mg, 0.89 mmol), Et3N (0.32 mL, 2.31 mmol), and H2O (0.15 mL) in THF (1.5 mL) at 0° C. under argon atmosphere. The reaction mixture was allowed to warm to rt and stirring was continued for 4 h. After removal of THF, the residue was partitioned between H2O and EtOAc (20/20 mL). The aqueous layer was further extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (20 mL), dried (MgSO4) and concentrated. Purification of the residue by flash chromatography (silica gel, 6:4 hexanes/EtOAc) yielded 1-[4-(5-bromopentyloxy)-5-methoxy-2-nitro-benzoyl]-4-methylene-L-proline methyl ester 18 as light yellow oil (rotamers): 1HNMR (300 MHz, CDCl3, rotamers) δ 1.62-1.68 (m, 2H), 1.86-1.98 (m, 4H), 2.64-2.75 (m, 1H), 2.99-3.08 (m, 1H), 3.43 (t, J=5.1 Hz, 2H), 3.59-3.96 (m, 7H), 4.05-4.21 (m, 3H), 4.57-4.61 and 4.90-5.12 (m, 3H), 6.80 and 6.83 (2 s, 1H), 7.64 and 7.67 (2 s, 1H); EIMS m/z 507 and 509 ([M]++Na).

後処理

  1. customExcess THF and oxalyl chloride were removed with rotavapor
  2. temperatureto warm to rt
  3. stirringstirring
  4. waitwas continued for 4 h
  5. customAfter removal of THF
  6. customthe residue was partitioned between H2O and EtOAc (20/20 mL)
  7. extractionThe aqueous layer was further extracted with EtOAc (3×10 mL)
  8. washThe combined organic layers were washed with brine (20 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated
  11. customPurification of the residue by flash chromatography (silica gel, 6:4 hexanes/EtOAc)

出典と根拠

ORDレコード
ord-72a635a0d0d74d7db5c0d4c74bb441ac
出典データセット
uspto-grants-2012_04
特許番号
US08163736B2

反応ノート

読み込み中…