Pyridine → Acetamide

HRID 1740135Notes

Reaction equation

HRID 1740135 reaction equation
[C:1]([N:11]1[CH2:14][C:13]([CH3:30])([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[CH2:25][C@@H:24]([CH2:26][NH2:27])[O:23][C:22]3=[O:28])=[CH:17][C:16]=2[F:29])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].[N:31]1C=CC=[CH:33][CH:32]=1.[C:37](OC(=O)C)(=[O:39])[CH3:38]>ClCCl>[F:29][C:16]1[CH:17]=[C:18]([N:21]2[CH2:25][C@H:24]([CH2:26][NH:27][C:37](=[O:39])[CH3:38])[O:23][C:22]2=[O:28])[CH:19]=[CH:20][C:15]=1[C:13]1([CH3:30])[CH2:14][N:11]([C:1]([O:3][CH2:4][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[O:2])[CH2:12]1.[C:32]([NH2:31])(=[O:2])[CH3:33]

Participants

6

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 18684844HCID 18684844, compound

Product 2

HCID 178AcetamideHCID 15887415HCID 15887415, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The title compound was prepared as followed: (R)-(-)-N-carbobenzyloxy-3-methyl-3-[2-fluoro-4-[5-aminomethyl-2-oxo-3-oxazolidinyl]phenyl]azetidine was diluted with 220 mL dichloromethane, cooled to 0° C., and successively treated with 3.7 mL pyridine (46 mmol) and 1.8 mL acetic anhydride (19 mmol) with no observable change. The cooling bath was removed and the reaction mixture was warmed to room temperature for 16 hours. The visually unchanged solution was concentrated to a yellow foam, rediluted with 50 mL dichloromethane, and filtered to remove the remaining insoluble precipitate. The filtrate was purified by LC on 340 g (230-400) silica gel eluting with 2.5% methanol/ethyl acetate to afford 5.85 g (84%) of (S)-N-[[3-[3-fluoro-4-[1-(carbobenzyloxy)-3-methyl)-3-azetidinyl]-phenyl]-2-oxo-5-oxazolidinyl]methyl]-acetamide as a colorless glass. Rf 0.24 (2.5% methanol/ethyl acetate); [α]D -19° (c 0.9971, methanol); IR (mull) 1754, 1706, 1676, 1516, 1430, 1415, 1357, 1227, 1194, 1075 cm-1 ; 1H NMR (300 MHz, CDCl3) δ7.42 (dd, 1H, J=2.1 Hz, J=12.9 Hz, aromatic), 7.33 (m, 5H, aromatic), 7.13 (dd, 1H, J=2.2 Hz, J=8.5 Hz, aromatic), 7.04 (t, 1H, J=8.5 Hz, aromatic), 6.56 (bt, 1H, J=6.2 Hz, NH), 5.10 (s, 2H, Ph--CH2), 4.79 (m, 1H, methine), 4.30 (d, 2H, J=8.2 Hz, Ph--C--CH2a s), 4.01 (m, 3H, Ph--C--CH2b s, Ph--N--CH2a), 3.78 (dd, 1H, J=6.7 Hz, J=9.1 Hz, Ph--N--CH2b), 3.64 (m, 2H, NH--CH2 s), 2.02 (s, 3H, O=C--CH3), 1.60, (s, 3H, Ph--C--CH3); 13C NMR (75 MHz, CDCl3) 171.2, 160.3 (d, JCF =246 Hz), 156.6, 154.2, 137.9 (d, JCF =11 Hz), 136.5, 128.9 (d, JCF =14 Hz), 128.4, 127.9, 127.2 (d, JCF =7 Hz), 113.2 (d, JCF =2 Hz), 106.4 (d, JCF =28 Hz), 72.0, 66.6, 60.7, 60.3, 47.3, 41.7, 36.1, 28.1, 22.9; Anal. Calcd for C24H26N3O5F1 : C, 63.29; H, 5.75; N, 9.23. Found: C, 62.98; H, 5.96; N, 8.98.

Workup

  1. customThe cooling bath was removed
  2. temperaturethe reaction mixture was warmed to room temperature for 16 hours
  3. concentrationThe visually unchanged solution was concentrated to a yellow foam
  4. additionrediluted with 50 mL dichloromethane
  5. filtrationfiltered
  6. customto remove the remaining insoluble precipitate
  7. customThe filtrate was purified by LC on 340 g (230-400) silica gel eluting with 2.5% methanol/ethyl acetate

Sources & evidence

ORD record
ord-b4e1e2938aef4251ab79fb559d3c2160
Source dataset
uspto-grants-1999_10
Patent number
US05968962

Reaction notes

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