Potassium Carbonate → 1,1-Dimethylethyl {[3'-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylyl]methyl}carbamate

HRID 564476Notes

Reaction equation

HRID 564476 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+].Br[C:27]1[C:28]([F:42])=[C:29]([CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[CH:30]=[CH:31][CH:32]=1.[CH3:43][C:44]([Si:47]([CH3:60])([CH3:59])[O:48][CH2:49][C:50]1[CH:51]=[C:52](B(O)O)[CH:53]=[CH:54][CH:55]=1)([CH3:46])[CH3:45]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:46][C:44]([Si:47]([CH3:60])([CH3:59])[O:48][CH2:49][C:50]1[CH:51]=[C:52]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])[C:28]=2[F:42])[CH:53]=[CH:54][CH:55]=1)([CH3:43])[CH3:45]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 57813382[3-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acidHCID 57813399tert-Butyl 3-bromo-2-fluorobenzylcarbamate

Product 1

HCID 578134311,1-Dimethylethyl {[3'-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylyl]methyl}carbamateYield 34%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Pd(OAc)2 (88.9 mg, 0.39 mmol), PPh3 (415.0 mg, 1.6 mmol), K2CO3 (2.7 g, 19.8 mmol) and 1,1-dimethylethyl [(3-bromo-2-fluorophenyl)methyl]carbamate (4.0 g, 13.2 mmol) were suspended in 1,4-dioxane (50 mL). After the mixture was heated to 80° C. for 15 min, [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (4.2 g, 15.8 mmol) was added. Then the reaction mixture was stirred over night at 100° C. After cooled to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in CH2Cl2 (80 mL), then was washed with water (30 mL), brine (30 mL), and dried over Na2SO4. After the solvent was removed, the crude product was purified on Al2O3 column chromatography, eluting with PE/EA (20:1). 1.98 g of the product, 1,1-dimethylethyl {[3′-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-fluoro-3-biphenylyl]methyl}carbamate, was obtained (yield: 34%). 1H NMR (400 MHz, CDCl3): δ 0.12 (s, 6 H), 0.95 (s, 9 H), 4.42-4.43 (m, 2 H), 4.80 (s, 2 H), 4.96 (s, 1 H), 7.17-7.48 (m, 7 H); 13C NMR (400 MHz, CDCl3): δ −5.3, 18.4, 25.9, 28.3, 38.9, 64.8, 124.2, 125.4, 126.7, 127.6, 128.3, 128.7, 129.7, 129.2, 129.7, 135.4, 141.6, 155.8; HPLC: retention time: 4.630 min; purity: 99.4% (HPLC).

Workup

  1. temperatureAfter cooled to room temperature
  2. customthe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in CH2Cl2 (80 mL)
  4. washwas washed with water (30 mL), brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. customAfter the solvent was removed
  7. customthe crude product was purified on Al2O3 column chromatography
  8. washeluting with PE/EA (20:1)

Sources & evidence

ORD record
ord-eab07c9c0289424f9d8017e1214ac112
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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