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Triethylamine → Methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate

HRID 354308
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HRID 354308 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:9][CH:10]2[CH2:14][CH2:13][CH2:12][N:11]2[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[C:4]([F:22])[CH:3]=1.CCN(CC)CC.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CS(C)=O.CO.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:18]([O:17][C:15]([N:11]1[CH2:12][CH2:13][CH2:14][CH:10]1[CH2:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([C:15]([O:17][CH3:18])=[O:16])=[CH:3][C:4]=1[F:22])=[O:16])([CH3:21])([CH3:20])[CH3:19]
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7

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HCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 235119311-Bromo-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzene

생성물 1

HCID 23512180Methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate수율 124.5%

시약·촉매·용매 3

HCID 167845palladium(II) acetate
촉매
HCID 679Dimethyl Sulfoxide용매
HCID 887Methanol용매

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온도
70 °C

실험 절차

To a stirred solution of 1-bromo-4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzene (549.4 mg, 1.468 mmol) in DMSO (6 mL) and MeOH (5 mL) was added Et3N (448 ul, 3.229 mmol), Pd(OAc)2 (36.2 mg, 0.161 mmol), and 1,3-bis(diphenylphosphino)propane (66.4 mg, 0.161 mmol). To the mixture was induced CO gas for 10 min. The resulting mixture was stirred at 70° C. for 2 days under a current of CO. After the mixture was concentrated, the residue was diluted with EtOAc. The solution was washed with brine and dried over Na2SO4. The solvent was removed under a reduced pressure and the residue was chromatographed on silica-gel eluting with n-hexane:EtOAc (5:1, v/v) as eluent to afford 323.0 mg (62%) methyl 4-[1-(tert-butoxycarbonyl)-2-pyrrolidinyl]methoxy-3-fluorobenzoate as a pale yellow oil. 1H-NMR (400 m/z, CDCl3) δ1.47 (s, 9H), 1.87(br s, 1H), 1.95-2.10 (m, 3H), 3.34-3.44 (br m, 2), 3.89 (s,. 3H), 3.94 and 4.11-4.26 (br m each, 3H), 7.03-7.11 (m, 1H), 7.75-7.80 (m, 2H); MS (FAB) m/z 354 (M++1).

후처리

  1. customfor 10 min
  2. concentrationAfter the mixture was concentrated
  3. additionthe residue was diluted with EtOAc
  4. washThe solution was washed with brine
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed under a reduced pressure
  7. customthe residue was chromatographed on silica-gel
  8. washeluting with n-hexane:EtOAc (5:1

출처 및 근거

ORD 기록
ord-f0645b80915d450e83f26a20643e798e
출처 데이터셋
uspto-grants-2004_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06756378B2

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