(4S,5R)-3-({3-[3'-acetyl-4'-(benzyloxy)-4-methoxybiphenyl-3-yl]-6-azetidin-1-ylpyridin-2-yl}methyl)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one → (4S,5R)-3-{[3-(3'-acetyl-4'-hydroxy-4-methoxybiphenyl-3-yl)-6-azetidin-1-ylpyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1508580Notes

Reaction equation

HRID 1508580 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([C:26]3[C:27]([CH2:36][N:37]4[C@@H:41]([CH3:42])[C@@H:40]([C:43]5[CH:48]=[C:47]([C:49]([F:52])([F:51])[F:50])[CH:46]=[C:45]([C:53]([F:56])([F:55])[F:54])[CH:44]=5)[O:39][C:38]4=[O:57])=[N:28][C:29]([N:32]4[CH2:35][CH2:34][CH2:33]4)=[CH:30][CH:31]=3)[CH:19]=2)[CH:7]=[CH:8][C:9]=1[O:10]CC1C=CC=CC=1)(=[O:3])[CH3:2]>CCOC(C)=O.[Pd]>[C:1]([C:4]1[CH:5]=[C:6]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([C:26]3[C:27]([CH2:36][N:37]4[C@@H:41]([CH3:42])[C@@H:40]([C:43]5[CH:44]=[C:45]([C:53]([F:56])([F:55])[F:54])[CH:46]=[C:47]([C:49]([F:51])([F:52])[F:50])[CH:48]=5)[O:39][C:38]4=[O:57])=[N:28][C:29]([N:32]4[CH2:33][CH2:34][CH2:35]4)=[CH:30][CH:31]=3)[CH:19]=2)[CH:7]=[CH:8][C:9]=1[OH:10])(=[O:3])[CH3:2]

Participants

4

Reactant 1

HCID 86704626(4S,5R)-3-({3-[3'-acetyl-4'-(benzyloxy)-4-methoxybiphenyl-3-yl]-6-azetidin-1-ylpyridin-2-yl}methyl)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 86704628(4S,5R)-3-{[3-(3'-acetyl-4'-hydroxy-4-methoxybiphenyl-3-yl)-6-azetidin-1-ylpyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (4S,5R)-3-({3-[3′-acetyl-4′-(benzyloxy)-4-methoxybiphenyl-3-yl]-6-azetidin-1-ylpyridin-2-yl}methyl)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (EXAMPLE 257 Step A) (42 mg, 0.053 mmol) and 10% Pd/C (20 mg, 0.053 mmol) in EtOAc (2 ml) was degassed and flushed with H2 using a balloon. The mixture was stirred at RT under H2 for 6 hours, then, flushed with nitrogen, and filtered washing with EtOAc. The filtrate was concentrated and the residue purified by TLC eluting with 3:2 hexanes/EtOAc to afford the title compound. Mass spectrum (ESI) 700.2 (M+1). 1H NMR (500 MHz, CD3OD): (atropisomers) δ 8.05 (s, 1H); 7.96 (s, 1H); 7.91-7.70 (m, 3H); 7.61 (dd, J=2.3, 8.7 Hz, 1H); 7.49-7.36 (m, 2H); 7.13 (d, J=8.2 Hz, 1H); 6.98 (d, J=8.7 Hz, 1H); 6.38 (d, J=8.5 Hz, 1H); 5.70 (br d, J=75.7 Hz, 1H); 4.69 (m, 1H); 4.43-3.73 (m, 9H); 2.68 (s, 3H); 2.42 (m, 2H); 0.65 (br d, J=37.5 Hz, 3H).

Workup

  1. customwas degassed
  2. customflushed with H2 using a balloon
  3. customflushed with nitrogen
  4. filtrationfiltered
  5. washwashing with EtOAc
  6. concentrationThe filtrate was concentrated
  7. customthe residue purified by TLC
  8. washeluting with 3:2 hexanes/EtOAc

Sources & evidence

ORD record
ord-5072a33bb1a144afb1b7b937afeb5009
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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