Ethyl Acetate → HCID 86755240, compound

HRID 1637099Notes

Reaction equation

HRID 1637099 reaction equation
Cl.Cl.[F:3][C:4]1[CH:9]=[CH:8][C:7]([C@H:10]2[CH2:15][CH2:14][C@H:13]([N:16]3[CH2:20][CH2:19][C@@H:18]([NH2:21])[CH2:17]3)[CH2:12][CH2:11]2)=[CH:6][CH:5]=1.C(N(CC)[CH:26]([CH3:28])[CH3:27])(C)C.[N+](C1C=C[C:37]([O:40][C:41]([N:43]2[C@@H](C3C=CC(F)=C(F)C=3)[C@H](COC3CCCCO3)[O:45][C:44]2=O)=[O:42])=CC=1)([O-])=O.[C:65]([O:68][CH2:69][CH3:70])(=[O:67])[CH3:66]>O1CCCC1.CCCCCC>[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:11][CH2:12][CH:13]([N:16]3[CH2:20][CH2:19][C@@H:18]([NH:21][C:44]([N:43]4[CH:70]([CH2:69][O:68][CH:65]5[CH2:66][CH2:27][CH2:26][CH2:28][O:67]5)[CH2:37][O:40][C:41]4=[O:42])=[O:45])[CH2:17]3)[CH2:14][CH2:15]2)=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 69945708HCID 69945708, compoundHCID 178478748HCID 178478748, compound

Product 1

HCID 86755240HCID 86755240, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Procedure

To a solution of trans-1-[4-(4-fluorophenyl)cyclohexyl]-(3R)-pyrrolidin-3-ylamine dihydrochloride (210 mg, 0.63 mmol) in dry tetrahydrofuran (4 mL) was added N,N-diisopropylethylamine (219 μL, 1.26 mmol) followed by (4S,5R)-4-(3,4-difluorophenyl)-2-oxo-5-(tetrahydropyran-2-yloxymethyl)-oxazolidine-3-carboxylic acid 4-nitrophenyl ester (300 mg, 0.63 mmol). The reaction mixture was stirred at ambient temperature for 18 h when the volatiles were removed under reduced pressure and residue dissolved in ethyl acetate (100 mL) and washed with 10% aqueous sodium carbonate solution (8×100 ml), brine (1×100 ml), dried over magnesium sulfate and filtered. The volatiles were removed under reduced pressure and the resulting oil was purified by pressurized silica gel chromatography (3:1 then 1:0 ethyl acetate:hexane to afford (4S,5R)-trans-4-(3,4-difluorophenyl)-5-(tetrahydropyran-2-yloxymethyl-2-oxo-oxazolidine-3-carboxylic acid {1-[4-(4-fluorophenyl)cyclohexyl]-(3R)-pyrrolidin-3-yl}amide as a white foam (153 mg, 0.25 mmol, 40%).

Workup

  1. customwere removed under reduced pressure and residue
  2. dissolutiondissolved in ethyl acetate (100 mL)
  3. washwashed with 10% aqueous sodium carbonate solution (8×100 ml), brine (1×100 ml)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customThe volatiles were removed under reduced pressure
  7. customthe resulting oil was purified by pressurized silica gel chromatography (3:1

Sources & evidence

ORD record
ord-0bbf5079640a413a9a30815cf4f6f108
Source dataset
uspto-grants-2000_03
Patent number
US06037354

Reaction notes

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