Tetrahydrofuran → methyl 3-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanoate

HRID 1508562Notes

Reaction equation

HRID 1508562 reaction equation
[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8](Br)=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][C:39]([CH2:42][CH2:43][C:44]([O:46][CH3:47])=[O:45])=[CH:38][C:37]=1B1OC(C)(C)C(C)(C)O1.C1COCC1.C([O-])([O-])=O.[K+].[K+]>C(OCC)(=O)C.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[N:1]1([C:5]2[N:10]=[C:9]([CH2:11][N:12]3[C@@H:16]([CH3:17])[C@@H:15]([C:18]4[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=4)[O:14][C:13]3=[O:32])[C:8]([C:41]3[CH:40]=[C:39]([CH2:42][CH2:43][C:44]([O:46][CH3:47])=[O:45])[CH:38]=[CH:37][C:36]=3[O:35][CH3:34])=[CH:7][CH:6]=2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 67036621Methyl 3-(4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoateHCID 86704598(4S,5R)-3-[(6-azetidin-1-yl-3-bromopyridin-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 56968291methyl 3-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanoate

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with (4S,5R)-3-[(6-azetidin-1-yl-3-bromopyridin-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (134 mg, 0.249 mmol), methyl 3-[4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propanoate (100 mg, 0.312 mmol), 1,1′-bis(di-t-butylphosphino)ferrocene palladium dichloride (8.11 mg, 0.012 mmol), and THF (3 mL). The reaction was degassed with N2 then 1M K2CO3 (3 mL, 3.00 mmol) was added. The reaction was stirred at room temperature for 45 min. The reaction was then diluted with ethyl acetate (20 mL), washed with water (2×15 mL) and brine (15 mL), dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel (0 to 100% ethyl acetate/hexanes) to afford methyl 3-{3-[6-azetidin-1-yl-2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)pyridin-3-yl]-4-methoxyphenyl}propanoate. LCMS=652.2 (M+H)+. 1H NMR (CDCl3, 500 MHz) δ 7.84 (s, 1H), 7.72 (s, 2H), 7.29 (d, J=8.4 Hz, 1H), 7.15 (dd, J=8.3, 2.2 Hz, 1H), 6.97 (bs, 1H), 6.86 (d, J=8.5 Hz, 1H), 6.26 (d, J=8.4 Hz, 1H), 5.57 (bs, 1H), 4.75 (m, 1H), 4.33-3.95 (m, 6H), 3.75 (s, 3H), 3.64 (s, 3H), 2.91 (m, 2H), 2.62 (m, 2H), 2.40 (m, 2H), 0.66-0.59 (m, 3H).

Workup

  1. customThe reaction was degassed with N2
  2. washwashed with water (2×15 mL) and brine (15 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel (0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-29ce65dc620c425ba923346fdc8511b8
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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