Sodium Carbonate → tert-Butyl 4-(3-((4-((S)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-(isoxazol-3-yl)-3-oxopropyl)phenoxy)methyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 2235615Notes

Reaction equation

HRID 2235615 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:39])[CH2:15][C@@H:16]([C:22]1[CH:38]=[CH:37][C:25]([O:26][CH2:27][C:28]2[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=2)=[CH:24][CH:23]=1)[C:17]1[CH:21]=[CH:20][O:19][N:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.FC(F)(F)S(O[C:46]1[CH2:51][CH2:50][N:49]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:48][CH:47]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Li+]>O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:39])[CH2:15][C@@H:16]([C:22]1[CH:38]=[CH:37][C:25]([O:26][CH2:27][C:28]2[CH:29]=[C:30]([C:46]3[CH2:51][CH2:50][N:49]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:48][CH:47]=3)[CH:31]=[CH:32][CH:33]=2)=[CH:24][CH:23]=1)[C:17]1[CH:21]=[CH:20][O:19][N:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 593007153-((4-((S)-3-((S)-4-Benzyl-2-oxooxazolidin-3-yl)-1-(isoxazol-3-yl)-3-oxopropyl)phenoxy)methyl)phenylboronic acid

Product 1

HCID 59300696tert-Butyl 4-(3-((4-((S)-3-((S)-4-benzyl-2-oxooxazolidin-3-yl)-1-(isoxazol-3-yl)-3-oxopropyl)phenoxy)methyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 7.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
85 °C

Procedure

To a sealed tube flushed with nitrogen and including DMF (0.5 mL), were added boronic acid 34.1 (90.0 mg, 0.171 mmol), triflate 34.3 (56.6 mg, 0.171 mmol), a 1 M sodium carbonate solution (0.48 mL, 0.480 mmol), lithium chloride (21.7 mg, 0.513 mmol), and Pd(dppf)Cl2 (13.9 mg, 0.0170 mmol). The reaction was heated and stirred at 85° C. for 1.5 hours. The reaction was then cooled and diluted with water. The mixture was extracted with EtOAc (2×50 mL). The organic layers were combined and washed with 1M lithium chloride (1×30 mL) and brine (1×30 mL), and dried over magnesium sulfate. The filtrate was concentrated, and the residue was purified by medium pressure chromatography (silica gel, 0 to 40% EtOAc:hexanes) to give 34.4 (8.90 mg). MS ESI (pos.) m/e: 664.3 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 8.21 (1H, d, J=1.6 Hz), 7.35 (1H, s), 7.09-7.30 (10H, m), 6.86 (2H, d, J=8.6 Hz), 6.06 (1H, d, J=1.6 Hz), 5.98 (1H, s), 4.95 (2H, s), 4.64-4.73 (1H, m), 4.49-4.60 (1H, m), 4.07 (2H, d, J=5.1 Hz), 3.99-4.03 (2H, m, J=2.7 Hz), 3.95 (1H, dd, J=17.6, 8.6 Hz), 3.56 (2H, t, J=5.7 Hz), 3.45 (1H, dd, J=17.4, 6.5 Hz), 3.13 (1H, dd, J=13.3, 3.1 Hz), 2.69 (1H, dd, J=13.5, 9.6 Hz), 2.42-2.50 (2H, m), 1.42 (9H, s).

Workup

  1. customTo a sealed tube flushed with nitrogen
  2. temperatureThe reaction was heated
  3. temperatureThe reaction was then cooled
  4. extractionThe mixture was extracted with EtOAc (2×50 mL)
  5. washwashed with 1M lithium chloride (1×30 mL) and brine (1×30 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationThe filtrate was concentrated
  8. customthe residue was purified by medium pressure chromatography (silica gel, 0 to 40% EtOAc:hexanes)

Sources & evidence

ORD record
ord-c5bbe822fac0497599deeba114b1c671
Source dataset
uspto-grants-2010_05
Patent number
US07714008B2

Reaction notes

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