Diethyl Ether → (R)-tert-butyl 2-(3-fluoro-4-(trifluoromethyl)benzoyl)-pyrrolidine-1-carboxylate

HRID 2279456노트

반응식

HRID 2279456 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[C:4]([F:12])[CH:3]=1.CCOCC.C([Li])CCC.CON(C)[C:26]([C@H:28]1[CH2:32][CH2:31][CH2:30][N:29]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:27]>C1COCC1>[F:12][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][C:5]=1[C:8]([F:11])([F:10])[F:9])[C:26]([C@H:28]1[CH2:32][CH2:31][CH2:30][N:29]1[C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[O:27]

참가 물질

6

반응물 4

HCID 3283Diethyl EtherHCID 688299HCID 688299, 화합물HCID 27829044-Bromo-2-fluorobenzotrifluorideHCID 178418339Butyllithium

생성물 1

HCID 71247670(R)-tert-butyl 2-(3-fluoro-4-(trifluoromethyl)benzoyl)-pyrrolidine-1-carboxylate수율 35%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

To a solution of 4-bromo-2-fluoro-1-(trifluoromethyl)benzene (4.854 g, 19.98 mmol) and ether (50 mL) cooled to −78° C. was added butyl lithium (7.990 mL, 19.98 mmol) slowly over 10 min. The reaction was transferred via cannula to a solution of 74 (4.30 g, 16.65 mmol) in THF (50 mL) cooled to −78° C. The reaction was stirred for 10 min after all aryl lithium was added. The reaction was quenched with water and extracted with DCM. The organic layer was concentrated and the crude product purified by SiO2 chromatography eluting with an EtOAc/hexane (1 to 5% EtOAc). A close running impurity was not removed by this purification. A SiO2 column was run eluting with an Et2O/hexane gradient (1 to 3% Et2O). The impurity was still present and the compound was finally purified on a SP4 reverse phase column chromatography eluting with MeCN/water gradient (65 to 100% MeCN) to afford 2.105 g (33.2%) of (R)-tert-butyl 2-(3-fluoro-4-(trifluoromethyl)benzoyl)-pyrrolidine-1-carboxylate (76).

후처리

  1. additionwas added
  2. customThe reaction was quenched with water
  3. extractionextracted with DCM
  4. concentrationThe organic layer was concentrated
  5. customthe crude product purified by SiO2 chromatography
  6. washeluting with an EtOAc/hexane (1 to 5% EtOAc)
  7. customwas not removed by this purification
  8. washA SiO2 column was run eluting with an Et2O/hexane gradient (1 to 3% Et2O)
  9. customthe compound was finally purified on a SP4 reverse phase column chromatography
  10. washeluting with MeCN/water gradient (65 to 100% MeCN)

출처 및 근거

ORD 기록
ord-f5cb3ac9e2e14bca916f55fa7f956b94
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09133187B2

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