Binap, (A+-)- → {1-[3-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]azetidin-3-yl}methanol

HRID 2171716노트

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HRID 2171716 반응식
Br[C:2]1[C:3]([F:17])=[C:4]([CH:14]=[CH:15][CH:16]=1)[CH2:5][O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8].C([O:25][CH2:26][CH:27]1[CH2:30][NH:29][CH2:28]1)C1C=CC=CC=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>[Pd].C1(/C=C/C(=O)/C=C/C2C=CC=CC=2)C=CC=CC=1.[C].[Pd].CCO.CCOC(C)=O.C1(C)C=CC=CC=1>[Si:7]([O:6][CH2:5][C:4]1[C:3]([F:17])=[C:2]([N:29]2[CH2:30][CH:27]([CH2:26][OH:25])[CH2:28]2)[CH:16]=[CH:15][CH:14]=1)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]

참가 물질

10

반응물 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 534094693-[(Benzyloxy)methyl]azetidineHCID 86686195((3-Bromo-2-fluorobenzyl)oxy)(tert-butyl)dimethylsilane

생성물 1

HCID 86686251{1-[3-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]azetidin-3-yl}methanol수율 19.3%

시약·촉매·용매 5

HCID 15673654(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one palladium촉매HCID 178418390HCID 178418390, 화합물촉매HCID 702Ethanol용매HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

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온도
90 °C

실험 절차

Under argon atmosphere, [(3-bromo-2-fluorobenzyl)oxy](tert-butyl)dimethylsilane (5.5 g), 3-[(benzyloxy)methyl]azetidine (2.5 g), and toluene (50 ml) were mixed, and (1E,4E)-1,5-diphenylpenta-1,4-dien-3-one palladium (3:2) (900 mg), BINAP (1.8 g), and sodium tert-butoxide (2.5 g) were added thereto, followed by stirring at 90° C. for 3 hours. The reaction mixture was cooled to room temperature, and EtOAc were added thereto, followed by filtering using Celite as a filtration adjuvant. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/EtOAc). The purified product thus obtained was mixed with EtOH (40 ml), and 10% palladium carbon (1 g) was added thereto, followed by stirring at room temperature overnight under hydrogen atmosphere of 1 atm and filtering using Celite as a filtration adjuvant. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (CHCl3/MeOH) to obtain {1-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]azetidin-3-yl}methanol (885 mg).

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationby filtering
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customthe residue was purified by silica gel column chromatography (hexane/EtOAc)
  5. customThe purified product thus obtained
  6. additionwas added
  7. stirringby stirring at room temperature overnight under hydrogen atmosphere of 1 atm
  8. filtrationfiltering
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (CHCl3/MeOH)

출처 및 근거

ORD 기록
ord-649e86207c9c45af9153b3a735d3deba
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09051283B2

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