Ethanol → tert-Butyl 4-[5-(4-{(5S)-5-[(acetylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-2-fluorophenyl)-2-pyridinyl]-1-piperazinecarboxylate

HRID 1446083Notes

Reaction equation

HRID 1446083 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[F:21][C:22]1[CH:23]=[C:24]([N:37]2[CH2:41][C@H:40]([CH2:42][NH:43][C:44](=[O:46])[CH3:45])[O:39][C:38]2=[O:47])[CH:25]=[CH:26][C:27]=1B1OC(C)(C)C(C)(C)O1.CCO.C([O-])([O-])=O.[K+].[K+]>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].C1(C)C=CC=CC=1>[C:44]([NH:43][CH2:42][C@@H:40]1[O:39][C:38](=[O:47])[N:37]([C:24]2[CH:25]=[CH:26][C:27]([C:2]3[CH:3]=[CH:4][C:5]([N:8]4[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]4)=[N:6][CH:7]=3)=[C:22]([F:21])[CH:23]=2)[CH2:41]1)(=[O:46])[CH3:45]

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 10407282(S)-N-((3-(3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamideHCID 112447754-Boc-1-(5-bromo-2-pyridyl)piperazine

Product 1

HCID 68549816tert-Butyl 4-[5-(4-{(5S)-5-[(acetylamino)methyl]-2-oxo-1,3-oxazolidin-3-yl}-2-fluorophenyl)-2-pyridinyl]-1-piperazinecarboxylateYield 69%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of tert-Butyl 4-(5-bromo-2-pyridinyl)-1-piperazinecarboxylate (0.203 g, 0.593 mmol) and N-({(5S)-3-[3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methyl)acetamide (0.270 g, 0.714 mmol) in dmf (4 mL), EtOH (1.5 mL), toluene (2.5 mL) and K2CO3 (1 mL, 2 M, 2 mmol) was purged with nitrogen. PdCl2(dppf) (24 mg, 0.03 mmol) was added and the mixture was heated to 90° C. under nitrogen for 1 h, then partitioned between EtOAc and water. Column chromatography (EtOAc) gave the titled compound (0.210 g, 69%) as a white solid. APCI MS m/z 514 (M+H). 1H NMR (400 MHz, DMSO-d6) δ 8.32 (bs, 1H), 8.27 (t, J=5.9 Hz, 1H), 7.75 (ddd, J=8.9, 2.4, 1.7 Hz, 1H), 7.53-7.60 (m, 2H), 7.38 (dd, J=8.6, 2.2 Hz, 1H), 6.94 (d, J=8.9 Hz, 1H), 4.72-4.79 (m, 1H), 4.15 (t, J=9.1 Hz, 1H), 3.77 (dd, J=9.2, 6.5 Hz, 1H), 3.52-3.57 (m, 4H), 3.40-3.46 (m, 6H), 1.84 (s, 3H), 1.43 (s, 9H).

Workup

  1. customwas purged with nitrogen
  2. custompartitioned between EtOAc and water

Sources & evidence

ORD record
ord-ca27253987144bf68608a8ef9b2e2970
Source dataset
uspto-grants-2010_02
Patent number
US07666864B2

Reaction notes

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