Pyridine → HCID 15887415, compound

HRID 428735Notes

Reaction equation

HRID 428735 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].N1C=CC=CC=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

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 18684844HCID 18684844, compound

Product 1

HCID 15887415HCID 15887415, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

The title compound was prepared as follows: (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) δ 7.42 (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—CH2as), 4.01 (m, 3H, Ph—C—CH2bs, Ph—N—CH2a), 3.78 (dd, 1H, J=6.7 Hz, J=9.1 Hz, Ph—N—CH2b),3.64 (m, 2H, NH—CH2s), 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 title compound was prepared
  2. customThe cooling bath was removed
  3. temperaturethe reaction mixture was warmed to room temperature for 16 hours
  4. concentrationThe visually unchanged solution was concentrated to a yellow foam
  5. additionrediluted with 50 mL dichloromethane
  6. filtrationfiltered
  7. customto remove the remaining insoluble precipitate
  8. 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-7e99dab899324a4c88dd1fa3ef348015
Source dataset
uspto-grants-2001_11
Patent number
US06313307B1

Reaction notes

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