HCID 117974405, compound → HCID 117974589, compound

HRID 708981Notes

Reaction equation

HRID 708981 reaction equation
[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:36])[C@H:15]([CH2:28][C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=1)[C@@H:16]([OH:27])[C@@H:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])O[CH2:39][C:40]([CH3:46])=[CH:41]C(C)(C)C>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:1]([C@@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:14](=[O:36])[C@H:15]([CH2:28][C:29]1[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=1)[C@@H:16]([O:27][CH2:41][C:40]([CH3:46])=[CH2:39])[C@@H:17]([O:19][CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 117974405HCID 117974405, compoundHCID 131733888HCID 131733888, compound

Product 1

HCID 117974589HCID 117974589, compoundYield 75.1%

Reagents, catalysts & solvents 3

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
55 °C

Procedure

To a 250 mL round bottom flask were added (R)-4-benzyl-3-((2R,3R,4S)-4-(benzyloxy)-3-hydroxy-2-(4-methylbenzyl)pentanoyl)oxazolidin-2-one (11.2 g, 23 mmol) and anhydrous THF (145 mL). The solution was sparged with N2 for 5 min and then tris(dibenzylideneacetone)-dipalladium (0) (Pd2(dba)3; 2.10 g, 2.3 mmol) and 1,1′-bis(diphenylphosphino)ferrocene (dppf; 2.55 g, 4.59 mmol) were added, and the resulting dark solution was sparged with N2 for an additional 5 minutes. The reaction mixture was warmed to 55° C. under N2 and treated with a solution of tert-butyl(2-methylallyl) carbonate (7.9 g, 45.9 mmol) in THF (5 mL). The dark mixture was stirred at 55° C. for 1 h and then cooled to room temperature, The reaction mixture was filtered through paper, rinsing with CH2Cl2, and the filtrate was evaporated to give a dark oil. The oil was partially purified by flash chromatography (SiO2, 0→30% acetone/hexanes) to give (R)-4-benzyl-3-((2R,3R,4S)-4-(benzyloxy)-3-((2-methylallyl)oxy)-2-(4-methylbenzyl)pentanoyl)oxazolidin-2-one (9.36 g) as a yellow oil that is contaminated with dibenzylideneacetone (dba): 1H NMR (400 MHz, CDCl3) δ 7.22 (m, 10H), 7.02 (d, J=7.8 Hz, 2H), 6.87 (m, 2H), 5.06 (m, 1H), 4.91 (s, 1H), 4.77 (ddd, J=11.7, 9.3, 4.7 Hz, 1H), 4.64 (d, J=11.9 Hz, 1H), 4.31 (d, J=11.9 Hz, 1H), 4.16 (s, 2H), 3.96 (m, 1H), 3.74 (dd, J=9.2, 7.1 Hz, 1H), 3.62 (p, J=6.1 Hz, 1H), 3.41 (m, 2H), 2.85 (m, 2H), 2.70 (dd, J=13.7, 3.5 Hz, 1H), 2.26 (s, 3H), 2.17 (s, 3H), 1.49 (dd, J=13.7, 10.6 Hz, 1H), 1.34 (d, J=6.1 Hz, 3H); ESIMS m/z 565 ([M+Na]+).

Workup

  1. customThe solution was sparged with N2 for 5 min
  2. customthe resulting dark solution was sparged with N2 for an additional 5 minutes
  3. temperaturecooled to room temperature
  4. filtrationThe reaction mixture was filtered through paper
  5. washrinsing with CH2Cl2
  6. customthe filtrate was evaporated
  7. customto give a dark oil
  8. customThe oil was partially purified by flash chromatography (SiO2, 0→30% acetone/hexanes)

Sources & evidence

ORD record
ord-75a8e7aea57d4c4bb52d5e107525f476
Source dataset
uspto-grants-2015_11
Patent number
US09179674B2

Reaction notes

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