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

HRID 2171716Notes

Reaction equation

HRID 2171716 reaction equation
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]

Participants

10

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 5

HCID 15673654(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one palladiumCatalystHCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-649e86207c9c45af9153b3a735d3deba
Source dataset
uspto-grants-2015_06
Patent number
US09051283B2

Reaction notes

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