Methanol → HCID 16039297, compound

HRID 2252448Notes

Reaction equation

HRID 2252448 reaction equation
C[O:2][P:3]([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](C(C)(C)C)(C)C)[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)=[C:15]([OH:48])[CH:14]=2)[CH:10]=[CH:11][CH:12]=1)(=[O:6])[O:4]C.Br[Si](C)(C)C.CO>ClCCl>[F:32][C:29]1[CH:30]=[CH:31][C:26]([C@@H:25]([OH:33])[CH2:24][CH2:23][C@H:22]2[C:21](=[O:41])[N:20]([C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[C@@H:19]2[C:16]2[CH:17]=[CH:18][C:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([P:3](=[O:2])([OH:4])[OH:6])[CH:8]=3)=[CH:14][C:15]=2[OH:48])=[CH:27][CH:28]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 76113BromotrimethylsilaneHCID 86600749HCID 86600749, compound

Product 1

HCID 16039297HCID 16039297, compoundYield 44%

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}-3′-hydroxybiphenyl-3-yl)phosphonate (0.041 g, 0.059 mmol) in dry dichloromethane (5 mL) under nitrogen was cooled in ice and bromotrimethylsilane (0.030 mL, 0.30 mmol) was dripped in over 5 min. The reaction mixture was stirred at room temperature for 3 h, then methanol (1 mL) was added and the reaction was partitioned between water and 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, 30% to 59% 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}-3′-hydroxybiphenyl-3-yl)phosphonic acid as a white powder (0.014 g, 44%); 1H NMR (300 MHz, CD3OD) δ 8.0 (d, J=13.6 Hz, 1H), 6.9-7.8 (m, 15H), 5.17 (d, J=2.1 Hz, 1H), 4.63 (d, J=5.2 Hz, 1H), 3.15-3.25 (m, 1H), 1.8-2.1 (m, 4H) ppm; MS [M−H]+ 546, [2M−H]+ 1093.

Workup

  1. customwas dripped in over 5 min
  2. customthe reaction was partitioned between water and 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, 30% to 59% acetonitrile-0.1% trifluoroacetic acid in water)

Sources & evidence

ORD record
ord-eedc6a80eba14f289f77acc817c4795c
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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