Triethylamine → {4-[(2R,3R)-3-{[2-(2,3-dihydro-1H-inden-5-yl)-2-oxoethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid

HRID 1366318Notes

Reaction equation

HRID 1366318 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13]SC3C([N+]([O-])=O)=CC=CN=3)[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([O:32]C(C)(C)C)=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.Br[CH2:66][C:67]([C:69]1[CH:70]=[C:71]2[C:75](=[CH:76][CH:77]=1)[CH2:74][CH2:73][CH2:72]2)=[O:68]>CC(C)=O.O>[CH2:74]1[C:75]2[C:71](=[CH:70][C:69]([C:67](=[O:68])[CH2:66][S:13][C@H:10]3[C:11](=[O:12])[N:8]([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[C@@H:9]3[C:24]3[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([OH:32])=[O:31])=[CH:37][CH:38]=3)=[CH:77][CH:76]=2)[CH2:72][CH2:73]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 131941252-Bromo-1-(2,3-dihydro-1H-inden-5-yl)ethan-1-oneHCID 86639220{4-[(2R,3R)-1-(4-fluoro-phenyl)-3-(3-nitro-pyridin-2-yldisulfanyl)-4-oxo-azetidin-2-yl]-phenoxy}-acetic acid tert-butyl ester

Product 1

HCID 66934629{4-[(2R,3R)-3-{[2-(2,3-dihydro-1H-inden-5-yl)-2-oxoethyl]thio}-1-(4-fluorophenyl)-4-oxoazetidin-2-yl]phenoxy}acetic acid

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

To a solution of tert-butyl (4-{(2R,3R)-1-(4-fluorophenyl)-3-[(3-nitropyridin-2-yl)dithio]-4-oxoazetidin-2-yl}phenoxy)acetate (0.100 g, 0.179 mmol) in acetone (2 ml) and water (0.5 ml) was added triphenylphosphine (0.047 g, 0.179 mmol). After 30 minutes, the mixture was concentrated. To the residue was added dichloromethane (3 ml) followed by the addition of triethylamine (0.073 g, 0.717 mmol) and 2-bromo-1-(2,3-dihydro-1H-inden-5-yl)ethanone (0.107 g, 0.448 mmol). After 30 minutes, full conversion of the thiol had been achieved. The mixture was concentrated and to the residue was added formic acid (2 g) and trifluoroacetic acid (0.2 g). The mixture was allowed to stir at room temperature for 3 h. The crude product was purified through preparative HPLC using an eluent of 10-50% CH3CN in 0.1M NH4OAc buffer. Freeze drying of pure fractions afforded the desired compound. 1H NMR [(CD3)2SO), 400 MHz] δ1.96-2.04 (m, 2H), 2.83-2.89 (m, 4H), 4.23-4.34 (m, 5H), 5.09 (d, 1H), 6.76-7.74 (m, 11H).

Workup

  1. concentrationthe mixture was concentrated
  2. additionTo the residue was added dichloromethane (3 ml)
  3. waitAfter 30 minutes
  4. concentrationThe mixture was concentrated and to the residue
  5. additionwas added formic acid (2 g) and trifluoroacetic acid (0.2 g)
  6. customThe crude product was purified through preparative HPLC
  7. customFreeze drying of pure fractions

Sources & evidence

ORD record
ord-46947c522a0f488bb139cdea948d66ef
Source dataset
uspto-grants-2011_02
Patent number
US07893048B2

Reaction notes

Loading…