Potassium Carbonate → HCID 69256517, compound

HRID 2252431Notes

Reaction equation

HRID 2252431 reaction equation
[C:1]([O:4][C:5]1[CH:10]=[C:9](Br)[CH:8]=[CH:7][C:6]=1[C@@H:12]1[C@@H:15]([CH2:16][CH2:17][C@H:18]([O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C:14](=[O:34])[N:13]1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)(=[O:3])[CH3:2].[OH:41][C:42]1[CH:43]=[C:44](B(O)O)[CH:45]=[CH:46][CH:47]=1.C(=O)([O-])[O-].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[C:1]([O:4][C:5]1[CH:10]=[C:9]([C:46]2[CH:45]=[CH:44][CH:43]=[C:42]([OH:41])[CH:47]=2)[CH:8]=[CH:7][C:6]=1[C@@H:12]1[C@@H:15]([CH2:16][CH2:17][C@H:18]([O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C:14](=[O:34])[N:13]1[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 59643928HCID 59643928, compound

Product 1

HCID 69256517HCID 69256517, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

Using Suzuki coupling methodology, 5-Bromo-2-{(2S,3R)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-oxo-1-phenylazetidin-2-yl}phenyl acetate (100 mg, 0.16 mmol) was combined with 3-hydroxyphenyl boronic acid (29 mg, 0.21 mmol) with deoxygenated toluene (3 mL) and deoxygenated ethanol (1 mL). 2.0 M aqueous potassium carbonate (0.31 mL, 0.31 mmol) was added and the vessel was purged with nitrogen. Tetrakis(triphenylphosphine)palladium(0) (9 mg, 0.008 mmol) was added and the vessel purged again. The reaction was heated to 70° C. for 1.5 h, cooled, diluted with water and extracted with ethyl acetate (2×). The combined organic layers were washed with water, brine, dried over sodium sulfate, filtered, concentrated and purified by chromatography (40 g silica gel, 20% to 90% ethyl acetate-hexane) to afford 4-{(2S,3R)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-oxo-1-phenylazetidin-2-yl}-3′-hydroxybiphenyl-3-yl acetate (70 mg, 69% yield)); Rf 0.34 (1:2 ethyl acetate-hexane); 1H NMR (300 MHz, CDCl3) δ 7.34-7.17 (m, 10H), 7.06-6.90 (m, 5H), 6.79 (ddd, J=8.1, 2.5, 0.8 Hz, 1H), 6.03 (br s, 1H), 4.67 (d, J=2.3 Hz, 1H), 4.64 (t, J=5.6 Hz, 1H), 3.26 (ddd, J=4.8, 2.5, 2.4 Hz, 1H), 2.27 (s, 3H), 1.94-1.73 (m, 4H), 0.84 (s, 9H), −0.02 (s, 3H), −0.19 (s, 3H) ppm; MS [M−OSi(CH3)2C(CH3)3]+ 508.0.

Workup

  1. customdeoxygenated ethanol (1 mL)
  2. customthe vessel was purged with nitrogen
  3. customthe vessel purged again
  4. temperaturecooled
  5. additiondiluted with water
  6. extractionextracted with ethyl acetate (2×)
  7. washThe combined organic layers were washed with water, brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified by chromatography (40 g silica gel, 20% to 90% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-5677c67aa3f04e4a9222667e5e35f9eb
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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