Bromotrimethylsilane → HCID 11272558, compound

HRID 2252442Notes

Reaction equation

HRID 2252442 reaction equation
[Si]([O:8][C@H:9]([C:41]1[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=1)[CH2:10][CH2:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]1[C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([P:35](=[O:40])([O:38]C)[O:36]C)[CH:30]=2)=[CH:25][CH:24]=1)(C(C)(C)C)(C)C.Br[Si](C)(C)C>ClCCl>[F:47][C:44]1[CH:45]=[CH:46][C:41]([C@@H:9]([OH:8])[CH2:10][CH2:11][C@H:12]2[C:15](=[O:16])[N:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C@@H:13]2[C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[C:31]([P:35](=[O:36])([OH:40])[OH:38])[CH:30]=3)=[CH:25][CH:24]=2)=[CH:42][CH:43]=1

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 86600747HCID 86600747, compound

Product 1

HCID 11272558HCID 11272558, compoundYield 100.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 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 (0.32 g, 0.47 mmol) in dry dichloromethane (15 mL) under nitrogen was cooled in an ice bath and bromotrimethylsilane (0.30 mL, 2.27 mmol) was dripped in over 5 min. The reaction mixture was stirred at room temperature for 3 h, then poured into ice water (20 m]L) and extracted with ethyl acetate. The organic solution was washed successively with water (2×) and brine. The organic solution was dried over sodium sulfate, filtered and the solvent was removed by rotary evaporation under reduced pressure. The residue was purified by reverse-phase HPLC (Polaris C18-A 10 μ 250×21.2 mm column, 20% to 70% acetonitrile-0.1% trifluoroacetic acid in water) to afford (4′-{(2S,3R)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxo-1-phenylazetidin-2-yl}biphenyl-3-yl)phosphonic acid (0.25 g, 99%) as a white powder; 1H NMR (300 MHz, CD3OD) δ 8.04 (br d, J=14.2 Hz, 1H) 7.68 (d, J=8.5 Hz, 2H), 7.50(d, J=8.5 Hz, 2H), 7.0-7.8 (m, 12H), 4.93 (d, J=2.2 Hz, 1H), 4.63 (t, J=5.2 Hz, 1H), 3.1-3.2 (m, 1H), 1.8-2.1 (m, 4H) ppm; MS [M−H]− 531, [2M-H]− 1061.

Workup

  1. customwas dripped in over 5 min
  2. extractionextracted with ethyl acetate
  3. washThe organic solution was washed successively with water (2×) and brine
  4. dry with materialThe organic solution was dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed by rotary evaporation under reduced pressure
  7. customThe residue was purified by reverse-phase HPLC (Polaris C18-A 10 μ 250×21.2 mm column, 20% to 70% acetonitrile-0.1% trifluoroacetic acid in water)

Sources & evidence

ORD record
ord-f8e81e6490cb4f61bd3f47bdb2c139ad
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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