Ethanol → (5S)-{4'-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2'-fluoro-biphenyl-4-ylmethyl}-(3-fluoro-propyl)-carbamic acid tert-butyl ester

HRID 341151Notes

Reaction equation

HRID 341151 reaction equation
C([C:5]([N:7]([CH2:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1)[CH2:8][CH2:9][CH2:10][F:11])=[O:6])(C)(C)C.CC[OH:24].[F:25][C:26]1[CH:27]=[C:28]([N:33]2[CH2:37][C@H:36]([CH2:38][NH:39][C:40](=[O:42])[CH3:41])[O:35][C:34]2=[O:43])[CH:29]=[CH:30][C:31]=1I.C([O-])([O-])=O.[K+].[K+].[C:50]1([CH3:56])[CH:55]=CC=C[CH:51]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[C:50]([O:24][C:5](=[O:6])[N:7]([CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:31]2[CH:30]=[CH:29][C:28]([N:33]3[CH2:37][C@H:36]([CH2:38][NH:39][C:40](=[O:42])[CH3:41])[O:35][C:34]3=[O:43])=[CH:27][C:26]=2[F:25])=[CH:17][CH:18]=1)[CH2:8][CH2:9][CH2:10][F:11])([CH3:56])([CH3:55])[CH3:51]

Participants

8

Reactant 5

HCID 702EthanolHCID 1140TolueneHCID 11430Potassium CarbonateHCID 11222662(S)-N-[3-(3-Fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamideHCID 219074294-(N-tert-butylcarbonyl-3-fluoropropylaminomethyl)phenyl boronic acid

Product 1

HCID 68540787(5S)-{4'-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2'-fluoro-biphenyl-4-ylmethyl}-(3-fluoro-propyl)-carbamic acid tert-butyl esterYield 61.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A suspension of aryl boronic acid 120 (25.0 g, 64.30 mmol, 1.45 equiv) in a mixture of toluene (120 mL), EtOH (40 mL), and water (40 mL) was treated with (5S)—N-[3-(3-fluoro-4-iodo-phenyl)-2-oxo-oxazolidin-5-ylmethyl]-acetamide 108 (16.80 g, 44.44 mmol, prepared as described in Example 1, above) and solid K2CO3 (18.40 g, 133.4 mmol, 3.0 equiv) at room temperature. The resulting reaction mixture was degassed three times under a steady stream of argon before being treated with Pd(PPh3)4 (2.57 g, 2.23 mmol, 0.05 equiv). The resulting reaction mixture was degassed three times under a steady stream of argon before being warmed to reflux for 8 h. When TLC and HPLC/MS showed the reaction was complete, the reaction mixture was cooled to room temperature before being poured into water (300 mL) and ethyl acetate (EtOAc, 300 mL). The two layers were separated, and the organic phase was washed with water (60 mL) and saturated aqueous NaCl (2×50 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The product was recrystallized from EtOAc/hexanes and dried in vacuo to afford the desired (5S)-{4′-[5-(acetylamino-methyl)-2-oxo-oxazolidin-3-yl]-2′-fluoro-biphenyl-4-ylmethyl}-(3-fluoro-propyl)-carbamic acid tert-butyl ester 121 (21.2 g, 61.5% yield for three steps) as an off-white powder.

Workup

  1. customThe resulting reaction mixture
  2. customwas degassed three times under a steady stream of argon
  3. customThe resulting reaction mixture
  4. customwas degassed three times under a steady stream of argon
  5. temperaturebefore being warmed
  6. temperatureto reflux for 8 h
  7. additionbefore being poured into water (300 mL) and ethyl acetate (EtOAc, 300 mL)
  8. customThe two layers were separated
  9. washthe organic phase was washed with water (60 mL) and saturated aqueous NaCl (2×50 mL)
  10. dry with materialdried over anhydrous Na2SO4
  11. concentrationconcentrated in vacuo
  12. customThe product was recrystallized from EtOAc/hexanes
  13. customdried in vacuo

Sources & evidence

ORD record
ord-56cc859db53f4deabf5d64486bf608be
Source dataset
uspto-grants-2014_11
Patent number
US08895741B2

Reaction notes

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