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

HRID 564482Notes

Reaction equation

HRID 564482 reaction equation
Br[C:2]1[C:3]([O:17][CH3:18])=[C:4]([CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:5]=[CH:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2OC)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:62][C:63]([Si:66]([CH3:79])([CH3:78])[O:67][CH2:68][C:69]1[CH:70]=[C:71](B(O)O)[CH:72]=[CH:73][CH:74]=1)([CH3:65])[CH3:64]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:65][C:63]([Si:66]([CH3:79])([CH3:78])[O:67][CH2:68][C:69]1[CH:70]=[C:71]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:3]=2[O:17][CH3:18])[CH:72]=[CH:73][CH:74]=1)([CH3:62])[CH3:64]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 16079156(1R)-Dicyclohexyl(2'-methoxy-[1,1'-binaphthalen]-2-yl)phosphaneHCID 57813344tert-butyl N-[(3-bromo-2-methoxyphenyl)methyl]carbamateHCID 57813382[3-({[(1,1-Dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid

Product 1

HCID 578135081,1-Dimethylethyl {[3'-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-(methyloxy)-3-biphenylyl]methyl}carbamateYield 72%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

1,1-Dimethylethyl {[3-bromo-2-(methyloxy)phenyl]methyl}carbamate (5.2 g, 16.4 mmol), Pd(OAc)2 (110.4 mg, 0.49 mmol), dicyclohexyl[2′-(methyloxy)-1,1′-binaphthalen-2-yl]phosphane (317.2 mg, 0.66 mmol) and K3PO4 (4.2 g, 19.7 mmol) were dissolved in dioxane (60 mL). The mixture was heated at 80° C. for 30 min, and then [3-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)phenyl]boronic acid (5.2 g, 19.7 mmol) was added. The mixture reaction was stirred at reflux overnight. The solvent was removed under reduced pressure, then diluted with CH2Cl2 (100 mL). The organic layer was washed with water (30 mL), brine (30 mL), and dried over Na2SO4. The product 1,1-dimethylethyl {[3′-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-(methyloxy)-3-biphenylyl]-methyl}carbamate (5.0 g) was purified by flash column chromatography (PE:EA=15:1). (Yield: 72%). 1H NMR (400 MHz, CDCl3): δ 0.11 (s, 6 H), 0.94 (s, 9 H), 1.46 (s, 9 H), 3.37 (s, 3 H), 4.40 (d, J=6 Hz, 2 H), 4.80 (s, 2 H), 5.04 (s, 1 H), 7.12-7.51 (m, 7 H); 13C NMR (100 MHz, CDCl3): δ −5.2, 18.4, 25.9, 28.4, 40.3, 60.4, 65.0, 124.2, 125.0, 126.6, 127.5, 128.3, 128.4, 130.6, 132.3, 134.8, 138.2, 141.5, 155.8; HPLC: retention time: 4.348 min; purity: 99.9%; MS: m/z 453 (M+), 344 (M+−TBS).

Workup

  1. customThe mixture reaction
  2. temperatureat reflux overnight
  3. customThe solvent was removed under reduced pressure
  4. additiondiluted with CH2Cl2 (100 mL)
  5. washThe organic layer was washed with water (30 mL), brine (30 mL)
  6. dry with materialdried over Na2SO4
  7. customThe product 1,1-dimethylethyl {[3′-({[(1,1-dimethylethyl)(dimethyl)silyl]oxy}methyl)-2-(methyloxy)-3-biphenylyl]-methyl}carbamate (5.0 g) was purified by flash column chromatography (PE:EA=15:1)

Sources & evidence

ORD record
ord-4bc5530b6f434777a9343a750e1644bb
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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