Diisopropylamine → HCID 178471783, compound

HRID 505302Notes

Reaction equation

HRID 505302 reaction equation
[Cl:1]C(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.C(NC(C)C)(C)C.[F:20][C:21]([F:64])([F:63])[C:22]1[CH:23]=[C:24]([C@H:32]2[O:36][C:35](=[O:37])[N:34]([CH2:38][C:39]3[C:44]([N:45]([CH2:48][C@H:49]4[CH2:54][CH2:53][C@H:52]([CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57])[CH2:51][CH2:50]4)[CH2:46][CH3:47])=[CH:43][CH:42]=[CH:41][N+:40]=3[O-])[C@H:33]2[CH3:62])[CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1>C(Cl)Cl.C([O-])(O)=O.[Na+]>[F:20][C:21]([F:64])([F:63])[C:22]1[CH:23]=[C:24]([C@H:32]2[O:36][C:35](=[O:37])[N:34]([CH2:38][C:39]3[C:44]([N:45]([CH2:48][C@H:49]4[CH2:54][CH2:53][C@H:52]([CH2:55][C:56]([O:58][CH2:59][CH3:60])=[O:57])[CH2:51][CH2:50]4)[CH2:46][CH3:47])=[CH:43][CH:42]=[C:41]([Cl:1])[N:40]=3)[C@H:33]2[CH3:62])[CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1

Participants

6

Reactant 3

HCID 7912Diisopropylamine2×HCID 94429Triphosgene2×HCID 178471788HCID 178471788, compound

Product 1

HCID 178471783HCID 178471783, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Triphosgene (360 mg, 1.21 mmol) and diisopropylamine (123 mg, 170 μL, 1.21 mol) were added successively to a stirred solution of ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-1-oxidopyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetate (156.6 mg, 0.243 mmol) in dry CH2Cl2 (9 mL) at −20° C. under N2. The reaction was stirred at room temperature for 6 h. Additional triphosgene (360 mg, 1.21 mmol) and diisopropylamine (123 mg, 170 μL, 1.21 mmol) were added successively and the reaction was stirred at room temperature overnight. The reaction was diluted with saturated NaHCO3 (10 mL) and extracted with CH2Cl2 (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 0-60% EtOAc in hexanes gradient) to afford ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6-chloropyridin-3-yl](ethyl)amino]methyl}cyclohexyl)acetate. Rf=0.32 (20% EtOAc/hexanes). LCMS calc.=664.2; found=664.4 (M+1)+. 1H NMR (500 MHz, CDCl3): δ 7.87 (s, 1 H); 7.81 (s, 2 H); 7.41 (d, J=8.4 Hz, 1 H); 7.19 (d, J=8.4 Hz, 1 H); 5.83 (d, J=8.4 Hz, 1 H); 4.97 (d, J=16.9 Hz, 1 H); 4.47-4.43 (m, 1 H); 4.29 (d, J=16.9 Hz, 1 H); 4.12-4.06 (m, 2 H); 2.98-2.88 (m, 2 H); 2.81-2.74 (m, 2H); 2.13 (d, J=6.8 Hz, 2 H); 1.84-1.68 (m, 5 H); 1.36-1.24 (m, 1 H); 1.22 (t, J=7.1 Hz, 3 H); 0.99 (t, J=7.0 Hz, 3 H); 0.95-0.81 (m, 4 H); 0.73 (d, J=6.6 Hz, 3 H).

Workup

  1. stirringthe reaction was stirred at room temperature overnight
  2. extractionextracted with CH2Cl2 (3×20 mL)
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThis was purified by flash chromatography (Si, 25×160 mm, 0-60% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-7918869105f8495389d5300ca3353280
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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