Diisopropylethylamine → ({[({(5s)-3-[4-(1,1-Dioxidotetrahydro-2h-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl} methyl)amino]carbonyl}oxy)methyl acetate

HRID 915268Notes

Reaction equation

HRID 915268 reaction equation
[NH2:1][CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[CH:13][C:12]([CH:15]3[CH2:20][CH2:19][S:18](=[O:22])(=[O:21])[CH2:17][CH2:16]3)=[C:11]([F:23])[CH:10]=2)[CH2:4]1.C(N(C(C)C)CC)(C)C.[C:33](Cl)(=[O:40])[O:34][CH2:35][O:36][C:37](=[O:39])[CH3:38]>C(Cl)Cl>[C:37]([O:36][CH2:35][O:34][C:33]([NH:1][CH2:2][C@@H:3]1[O:7][C:6](=[O:8])[N:5]([C:9]2[CH:14]=[CH:13][C:12]([CH:15]3[CH2:20][CH2:19][S:18](=[O:21])(=[O:22])[CH2:17][CH2:16]3)=[C:11]([F:23])[CH:10]=2)[CH2:4]1)=[O:40])(=[O:39])[CH3:38]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 14800978[(Chlorocarbonyl)oxy]methyl acetateHCID 54349937(5S)-(-)-3-[3-fluoro-4-(tetrahydro-1,1-dioxido-2H-thiopyran-4-yl)phenyl]-5-aminomethyl-2-oxazolidinone

Product 1

HCID 58958560({[({(5s)-3-[4-(1,1-Dioxidotetrahydro-2h-thiopyran-4-yl)-3-fluorophenyl]-2-oxo-1,3-oxazolidin-5-yl} methyl)amino]carbonyl}oxy)methyl acetateYield 165.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred suspension of the 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]-2-fluorophenyl}tetrahydro-1λ6-thiopyran-1,1(2H)-dione (4.68 g, 13.74 mmol) prepared according to the PCT international publication WO 97/09328 in CH2Cl2 (100 mL) cooled to 0° C. is added diisopropylethylamine (4.8 ml, 27.48 mmol) followed by a solution of 2.4 g (1.5 7 mmol) of the acid chloride (from Step 4) in CH2Cl2 (10 mL) with a 2 mL rinse. The reaction mixture is stirred at 0° C. fro 30 min then at RT for 3 h. The reaction mixture is partitioned between CH2Cl2 (300 mL) and H2O (200 mL). The phases are separated. The organics are washed with 1N HCl (100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated. The residue is dissolved in CH2Cl2, absorbed onto silca gel and purified on a Biotage 40M with a SIM using 2% CH3OH in CH2Cl2 as the eluent to afford 5.32 g (11.6 mmol, 85%) of the desired carbamate as a white foam. 1H NMR (DMSO) δ 7.96 (t, J=6 Hz, 1H), 7.48 (dd, J=14, 2 Hz, 1H), 7.38 (t, J=9 Hz, 1H), 7.24 (dd, J=9, 2 Hz, 1H), 5.61(s, 2H), 4.74 (m, 1H), 4.12 (t, J=9 Hz, 1H), 3.76 (dd, J=9, 7 Hz, 1H), 3.38 (m, 4 H), 3.16 (m, 1H), 3.11 (m, 2H), 2.13 (m, 2H), 2.06 (m, 1H), 2.01 (s, 3H); 13C NMR (DMSO-d6) δ 169.3, 160.6, 158 (d, J=246 Hz), 154.8, 153.8, 138.3 (d, J=8 Hz), 128.1, 125.2 (d, J=11 Hz), 113.7, 105.2 (d, J=26 Hz), 79.3, 71.7, 54.8, 50.3, 46.8, 43.1, 33.3, 29.8, 20.4; IR (diffuse reflectance) 2415, 2351, 2328, 1921, 1916, 1753, 1744, 1515, 1411, 1292, 1247, 1223, 1121, 1010, 983 cm−1. % Water (KF titration): 1.08. [a]25D=−36° (c 0.91, DMSO). Anal. Calcd for C19H23FN2O8S plus 1.08% H2O: C, 49.24; H, 5.12; N, 6.04; S, 6.85. Found: C, 49.05; H, 5.21; N, 5.81; S, 6.85.

Workup

  1. customprepared
  2. washrinse
  3. waitat RT for 3 h
  4. customThe reaction mixture is partitioned between CH2Cl2 (300 mL) and H2O (200 mL)
  5. customThe phases are separated
  6. washThe organics are washed with 1N HCl (100 mL), brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. dissolutionThe residue is dissolved in CH2Cl2
  11. customabsorbed onto silca gel
  12. custompurified on a Biotage 40M with a SIM

Sources & evidence

ORD record
ord-05e9b464ae6e44c090d7a0cf866b381b
Source dataset
uspto-grants-2007_09
Patent number
US07265140B2

Reaction notes

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