N,N,N',N'-Tetramethylethylenediamine → Methyl (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-fluoro-4-{[(2-fluorophenyl)methyl]oxy}phenyl)-5-oxopentanoate

HRID 2264808

반응식

HRID 2264808 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13](Br)=[C:12]([F:17])[CH:11]=1.CN(CCN(C)C)C.C([Li])CCC.[O:31]=[C:32]1[N:36]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C@H:35]([C:44]([O:46][CH3:47])=[O:45])[CH2:34][CH2:33]1>C1COCC1>[CH3:43][C:40]([O:39][C:37]([NH:36][C@@H:35]([CH2:34][CH2:33][C:32]([C:13]1[CH:14]=[CH:15][C:10]([O:9][CH2:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])=[CH:11][C:12]=1[F:17])=[O:31])[C:44]([O:46][CH3:47])=[O:45])=[O:38])([CH3:41])[CH3:42]

참가 물질

6

반응물 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 108684851-O-tert-butyl 2-O-methyl (2S)-5-oxopyrrolidine-1,2-dicarboxylateHCID 595967064-Bromo-3-fluorophenyl (2-fluorophenyl)methyl etherHCID 178418339Butyllithium

생성물 1

HCID 59596685Methyl (2S)-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-5-(2-fluoro-4-{[(2-fluorophenyl)methyl]oxy}phenyl)-5-oxopentanoate수율 39.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

To a solution of 4-bromo-3-fluorophenyl (2-fluorophenyl)methyl ether (D41, 500 mg, 1.67 mmol) and TMEDA (178 mg, 1.53 mmol) in dry THF (7 ml) at −78° C. under nitrogen atmosphere was added n-butyllithium 1.6M solution in hexanes (1 ml, 1.6 mmol) dropwise. The resulting suspension was stirred at −78° C. for 15 minutes and then it was added dropwise to a solution of 1-(1,1-dimethylethyl) 2-methyl (2S)-5-oxo-1,2-pyrrolidinedicarboxylate (D5, 338 mg, 1.39 mmol) in dry THF (2 ml). The mixture was stirred at −78° C. for 1 h, then it was quenched with a saturated ammonium chloride aqueous solution. The phases were separated and the organic layer was washed with brine, dried over Na2SO4, filtered, and evaporated under reduced pressure. The resulting residue was purified by chromatography on silica gel eluting with cyclohexane/ethylacetate (9:1 to 85:15) affording the title compound as a white solid (254 mg, 39%); 1H NMR (300 MHz, CDCl3-d) δ (ppm): 8.00-7.80 (m, 1H); 7.53-7.42 (m, 1H); 7.42-7.25 (m, 1H); 7.23-7.05 (m, 2H); 6.90-6.80 (m, 1H); 6.75-6.65 (m, 1H); 5.18 (s, 2H); 4.50-4.30 (m, 1H); 3.71 (s, 3H); 3.18-2.85 (m, 2H); 2.40-2.20 (m, 1H); 2.15-1.90 (m, 1H); 1.40 (s, 9H).

후처리

  1. stirringThe mixture was stirred at −78° C. for 1 h
  2. customit was quenched with a saturated ammonium chloride aqueous solution
  3. customThe phases were separated
  4. washthe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe resulting residue was purified by chromatography on silica gel eluting with cyclohexane/ethylacetate (9:1 to 85:15)

출처 및 근거

ORD 기록
ord-9454c9f091ee47ef87bc3b4daacd0b7b
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07855218B2

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