Triethylamine → HCID 86600747, compound

HRID 2252441Notes

Reaction equation

HRID 2252441 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]([C:13]2[CH:18]=[CH:17][C:16]([C@@H:19]3[C@@H:22]([CH2:23][CH2:24][C@H:25]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[C:26]4[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=4)[C:21](=[O:41])[N:20]3[C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[CH:15][CH:14]=2)[CH:10]=[CH:11][CH:12]=1)(=O)=O.[P:50]([O-:55])([O:53][CH3:54])[O:51][CH3:52].C(N(CC)CC)C>C1(C)C=CC=CC=1>[Si:34]([O:33][C@H:25]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[CH2:24][CH2:23][C@H:22]1[C:21](=[O:41])[N:20]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[C@@H:19]1[C:16]1[CH:15]=[CH:14][C:13]([C:9]2[CH:8]=[CH:7][CH:12]=[C:11]([P:50](=[O:55])([O:53][CH3:54])[O:51][CH3:52])[CH:10]=2)=[CH:18][CH:17]=1)([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 21884954DimethylphosphiteHCID 59643970HCID 59643970, compound

Product 1

HCID 86600747HCID 86600747, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
160 °C

Procedure

This reaction was performed using a PersonalChemistry™ microwave instrument set at normal absorbance, fixed hold time and 30 sec pre-stirring. A 10-mL reaction vial was charged with 4′-{(2S,3R)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-oxo-1-phenylazetidin-2-yl}biphenyl-3-yl trifluoromethanesulfonate (0.27 g, 0.38 mmol), dimethyl phosphite (0.070 mL, 0.76 mmol) and triethylamine (0.15 mL, 1.08 mmol) in toluene (4 mL). Nitrogen was bubbled through the stirred solution for 5 min, tetrakis(triphenylphosphine)palladium(0) (0.1 g) was added, and the solution was covered with a blanket of nitrogen and sealed. The reaction mixture was heated for 11 min at 160° C., then cooled to room temperature and diluted with ethyl acetate. The yellow solution was washed successively with 0.5 M hydrochloric acid (20 mL) water (3×) and brine. The organic solution was dried over sodium sulfate, filtered and the solvent was removed by rotary evaporation under reduced pressure. Pure dimethyl (4′-{(2S,3R)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-oxo-1-phenylazetidin-2-yl}biphenyl-3-yl)phosphonate was obtained as a white foam (0.26 g, 65%) by chromatography over silica gel using ethyl acetate-hexane (gradient: 5% ethyl acetate to 100%). 1H NMR (300 MHz, CDCl3) δ 8.00 (dt, J=14.2, 1.5 Hz, 1H), 7.60 (d, J=8.5 Hz, 2H), 7.40(d, J=8.5 Hz, 2H), 6.9-7.8 (m, 12H), 4.68 (t, J=5.7 Hz, 1H), 4.64 (d, J=2.4 Hz, 1H), 3.81 (d, J=0.9 Hz, 1H), 3.77 (d, J=0.9 Hz, 1H), 3.0-3.1 (m, 1H), 1.8-2.2 (m, 4H), 0.88 (s, 9H), 0.02 (s, 3H), −0.16 (s, 3H) ppm

Workup

  1. customhold time and 30 sec
  2. customA 10-mL reaction
  3. customNitrogen was bubbled through the stirred solution for 5 min
  4. additiontetrakis(triphenylphosphine)palladium(0) (0.1 g) was added
  5. customsealed
  6. temperaturecooled to room temperature
  7. additiondiluted with ethyl acetate
  8. washThe yellow solution was washed successively with 0.5 M hydrochloric acid (20 mL) water (3×) and brine
  9. dry with materialThe organic solution was dried over sodium sulfate
  10. filtrationfiltered
  11. customthe solvent was removed by rotary evaporation under reduced pressure

Sources & evidence

ORD record
ord-f8d63b652dc147a19ea106110dbad6ef
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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