Triphenylphosphine → Sodium (5R,6S)-2-(5-Ethyl-1-methylpyrazol-3-yl)-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate

HRID 1825363Notes

Reaction equation

HRID 1825363 reaction equation
[CH2:1]([C:3]1[N:7]([CH3:8])[N:6]=[C:5]([C:9]2[CH2:10][C@@H:11]3[C@@H:21]([C@H:22]([OH:24])[CH3:23])[C:20](=[O:25])[N:12]3[C:13]=2[C:14]([O:16]CC=C)=[O:15])[CH:4]=1)[CH3:2].C(OCC)(=O)C.ClCCl.C(C(CCCC)C([O-])=O)C.[Na+:45].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>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.CC(C)=O.C(OCC)(=O)C>[CH2:1]([C:3]1[N:7]([CH3:8])[N:6]=[C:5]([C:9]2[CH2:10][C@@H:11]3[C@@H:21]([C@H:22]([OH:24])[CH3:23])[C:20](=[O:25])[N:12]3[C:13]=2[C:14]([O-:16])=[O:15])[CH:4]=1)[CH3:2].[Na+:45]

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 21226138Dichloromethane ethylacetateHCID 23672331Sodium 2-ethylhexanoateHCID 131719868Allyl (5R,6S)-2-(5-Ethyl-1-methylpyrazol-3-yl)-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate

Product 1

HCID 131719869Sodium (5R,6S)-2-(5-Ethyl-1-methylpyrazol-3-yl)-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylateYield 95.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 21584569Ethylacetate acetoneSolvent

Procedure

Allyl (5R,6S)-2-(5-ethyl-1-methylpyrazol-3-yl)-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (348 mg) in 1:1 ethyl acetate/dichloromethane (8 ml), under argon was treated successively with sodium 2-ethylhexanoate (198 mg), triphenylphosphine (27 mg) and tetrakis(triphenylphosphine)palladium (0), (38 mg). After a few seconds an off-white precipitate was formed. The reaction mixture was stirred at room temperature for 30 m. T.l.c. analysis (20% acetone/ethyl acetate showed no remaining starting material. The solvents were removed in vacuo and the residual solid stirred with diethyl ether (20 ml). The white solid was filtered off washed with ether and dried. This solid was dissolved in water (10 ml) and chromatographed on HP20SS resin eluting with 1-5% tetrahydrofuran/water (100 ml portions). The combined fractions containing the product (by h.p.l.c.), were concentrated and freeze-dried to give the title compound as an amorphous pale yellow solid, (314 mg, 95%); nmax (KBr) 1755, 1614, 1586 and 1386 cm−1; dH(D2O) 1.17 (3H, t, J7.5 Hz), 1.26 (3H, d, J6.4 Hz), 2.56 (2H, q, J7.5 Hz), 3.16 (2H, m), 3.44 (1H, dd, J2.8,6.0 Hz), 3.68 (3H, s), 4.21 (2H, m) and 6.47 (1H, s). m/z (Electrospray) 328 (MH+), 350 (MNa+), 633 (2MNa+, free acid), 655 (2MH+), 677 (2MNa+).

Workup

  1. customAfter a few seconds an off-white precipitate was formed
  2. customThe solvents were removed in vacuo
  3. stirringthe residual solid stirred with diethyl ether (20 ml)
  4. filtrationThe white solid was filtered off
  5. washwashed with ether
  6. customdried
  7. dissolutionThis solid was dissolved in water (10 ml)
  8. customchromatographed on HP20SS resin
  9. washeluting with 1-5% tetrahydrofuran/water (100 ml portions)
  10. additionThe combined fractions containing the product (by h.p.l.c.)
  11. concentrationwere concentrated
  12. customfreeze-dried

Sources & evidence

ORD record
ord-4e8ed3a729924e6b9c6ebf26e3dd366e
Source dataset
uspto-grants-2006_05
Patent number
US07045619B2

Reaction notes

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