Sodium Hydroxide → HCID 59570886, compound

HRID 2192907Notes

Reaction equation

HRID 2192907 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]([CH:16]([CH2:20][C@H:21]3[CH2:41][CH2:40][C:23]4([O:27][C@H:26]([C:28]5[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=5)[C@@H:25]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=5)[O:24]4)[CH2:22]3)[C:17](O)=[O:18])[CH:7]=[CH:8][C:9]=2[S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])[CH2:3][CH2:2]1.CC(C)(C)C(Cl)=O.[CH2:49]([C@@H:56]1[CH2:60][O:59][C:58](=[O:61])[NH:57]1)[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1.C([Li])CCC.CCCCCC.[OH-].[Na+]>C1COCC1.C(N(CC)CC)C>[CH2:49]([C@@H:56]1[CH2:60][O:59][C:58](=[O:61])[N:57]1[C:17](=[O:18])[CH:16]([C:6]1[CH:7]=[CH:8][C:9]([S:10]([CH:13]2[CH2:15][CH2:14]2)(=[O:12])=[O:11])=[C:4]([CH:1]2[CH2:2][CH2:3]2)[CH:5]=1)[CH2:20][C@H:21]1[CH2:41][CH2:40][C:23]2([O:27][C@H:26]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C@@H:25]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)[O:24]2)[CH2:22]1)[C:50]1[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=1

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 62493Pivaloyl chlorideHCID 2734969(R)-4-Benzyl-2-oxazolidinoneHCID 59570904HCID 59570904, compoundHCID 178418244HCID 178418244, compound

Product 1

HCID 59570886HCID 59570886, compoundYield 79.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Procedure

To a solution of 2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7R)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]propionic acid (70.8 g) in THF (350 mL) were added triethylamine (21 mL) and 2,2-dimethylpropanoyl chloride (19 mL) at an internal temperature of 11° C. or lower under ice-cooling, followed by stirring at room temperature for 1 hour. In another vessel, to a solution of (4R)-4-benzyl-1,3-oxazolidin-2-one (26.3 g) in THF (200 mL) was added 2.64 M n-butyl lithium/hexane solution (54.8 mL) at an internal temperature of −50° C. or lower, followed by warming to room temperature, stirring for 1 hour, and then cooling to an internal temperature of −60° C. To this reaction mixture was added dropwise the acid anhydride/THF mixture, which had been prepared previously, at an internal temperature of −50° C. or lower, followed by stirring at room temperature for 4 hours. 1 M Sodium hydroxide (600 mL) was added thereto under ice-cooling and the organic solvent was evaporated under reduced pressure, followed by extraction with ethyl acetate/hexane (1/3, 200 mL×3). The organic layer was sequentially washed with a saturated aqueous ammonium chloride solution (200 mL) and saturated brine (200 mL), and dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure to obtain (4R)-4-benzyl-3-{2-[3-cyclopropyl-4-(cyclopropylsulfonyl)phenyl]-3-[(2R,3R,7R)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]propanoyl}-1,3-oxazolidin-2-one (72 g) as a brown oil.

Workup

  1. temperaturelower under ice-cooling
  2. temperatureby warming to room temperature
  3. stirringstirring for 1 hour
  4. temperaturecooling to an internal temperature of −60° C
  5. customhad been prepared previously, at an internal temperature of −50° C.
  6. stirringby stirring at room temperature for 4 hours
  7. temperatureunder ice-cooling
  8. customthe organic solvent was evaporated under reduced pressure
  9. extractionfollowed by extraction with ethyl acetate/hexane (1/3, 200 mL×3)
  10. washThe organic layer was sequentially washed with a saturated aqueous ammonium chloride solution (200 mL) and saturated brine (200 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. customthe solvent was then evaporated under reduced pressure

Sources & evidence

ORD record
ord-5cbd99d55c2c4e64ab6c4ff595f3a7b0
Source dataset
uspto-grants-2012_12
Patent number
US08329707B2

Reaction notes

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