Triethylamine → HCID 67145028, 화합물

HRID 1695320노트

반응식

HRID 1695320 반응식
[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]

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 11002937HCID 11002937, 화합물HCID 450899474-Methylene-L-proline methyl ester

생성물 1

HCID 67145028HCID 67145028, 화합물

시약·촉매·용매 3

HCID 6228Dimethylformamide촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-72a635a0d0d74d7db5c0d4c74bb441ac
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08163736B2

반응 노트

불러오는 중…