Ethyl Acetate → HCID 57055185, compound

HRID 1856662Notes

Reaction equation

HRID 1856662 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[CH:20]=[CH:19][CH:18]=[CH:17][C:14]=3[C:15]#[N:16])[CH2:9][CH2:8]2)[CH2:3]1.C(N(CC)C(C)C)(C)C.[N+](C1C=CC([O:39][C:40]([N:42]2[C@@H:46]([C:47]3[CH:52]=[CH:51][C:50]([F:53])=[C:49]([F:54])[CH:48]=3)[C@H:45]([CH2:55][O:56][CH:57]3[CH2:62][CH2:61][CH2:60][CH2:59][O:58]3)[O:44][C:43]2=[O:63])=O)=CC=1)([O-])=O.C(OCC)(=O)C>CCCCCC>[C:15]([C:14]1[CH:17]=[CH:18][CH:19]=[CH:20][C:13]=1[N:10]1[CH2:11][CH2:12][CH:7]([N:4]2[CH2:5][CH2:6][C@@H:2]([NH:1][C:40]([N:42]3[C@@H:46]([C:47]4[CH:52]=[CH:51][C:50]([F:53])=[C:49]([F:54])[CH:48]=4)[C@H:45]([CH2:55][O:56][CH:57]4[CH2:62][CH2:61][CH2:60][CH2:59][O:58]4)[O:44][C:43]3=[O:63])=[O:39])[CH2:3]2)[CH2:8][CH2:9]1)#[N:16]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 54388801HCID 54388801, compoundHCID 69945708HCID 69945708, compound

Product 1

HCID 57055185HCID 57055185, compoundYield 59.1%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

To a solution of 2-[4-(3-amino-(3R)-pyrrolidin-1-yl)piperidin-1-yl]benzonitrile (166 mg, 0.44 mmol) in dry, degassed N,N-dimethylformamide (4 mL) was added N,N-diisopropylethylamine (230 μL, 1.3 mmol) followed by (4S,5R)-4-(3,4-difluorophenyl)-2-oxo-5-(tetrahydropyran-2-yloxymethyl)-oxazolidine-3-carboxylic acid 4-nitrophenyl ester (210 mg, 0.44 mmol). The reaction mixture was stirred at room temperature for 4 h when the volatiles were removed under reduced pressure, the residue dissolved in ethyl acetate (100 mL), 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 (1:1 then 2:1 ethyl acetate:hexane) to afford (4S,5R)-4-(3,4-difluorophenyl)-2-oxo-5-(tetrahydropyran-2-yloxymethyl)oxazolidine-3-carboxylic acid {1-[1-(2-cyanophenyl)piperidin-4-yl]-(3R)-pyrrolidin-3-yl}amide as a white foam (156 mg, 0.26 mmol, 59%).

Workup

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

Sources & evidence

ORD record
ord-c7b1b84511134f389dfd570ed4634bdf
Source dataset
uspto-grants-2000_11
Patent number
US06143750

Reaction notes

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