Hydrochloric Acid → (S)-tert-butyl 2,2-dimethyl-4-(3-((R)-4-methyl-2-oxooxazolidin-3-yl)-3-oxopropyl)oxazolidine-3-carboxylate

HRID 218408Notes

Reaction equation

HRID 218408 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH2:14][C:15]([OH:17])=O)[CH2:11][O:10][C:9]1([CH3:19])[CH3:18])=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:22]([CH2:25]C)CC)C.[C:27](Cl)(=[O:32])[C:28](C)(C)[CH3:29].[Li+].[Cl-].Cl.C1C[O:40]CC1>>[CH3:18][C:9]1([CH3:19])[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C@@H:12]([CH2:13][CH2:14][C:15]([N:22]2[C@H:28]([CH3:29])[CH2:27][O:32][C:25]2=[O:40])=[O:17])[CH2:11][O:10]1

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 433294Lithium ChlorideHCID 10635974(S)-3-Boc-2,2-dimethyloxazolidine-4-propanoic Acid

Product 1

HCID 67379968(S)-tert-butyl 2,2-dimethyl-4-(3-((R)-4-methyl-2-oxooxazolidin-3-yl)-3-oxopropyl)oxazolidine-3-carboxylate

Conditions

Temperature
0 °C

Procedure

A 2000 mL flask was charged with (S)-3-(3-(tert-butoxycarbonyl)-2,2-dimethyloxazolidin-4-yl)propanoic acid (21.6 g, 79 mmol) and 750 mL of dry THF. The solution was cooled to 0° C., then triethylamine (23.94 g, 237 mmol, 3.0 equiv) and pivaloyl chloride (9.76 mL, 79 mmol, 1.0 equiv) were sequentially added. The solution was stirred for 4 hr at 0° C. After this time (R)-4-benzyl-2-oxalozolidinone (13.26 g, 75.2 mmol, 0.95 equiv) and dried LiCl (3.68 g, 86.4 mmol, 1.1 equiv) were added and the reaction was allowed to stir for 13 hr with concomitant warming to ambient temperature. After this time 560 mL of 0.5 M HCl was added, the mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with EtOAc (3×370 mL), and the combined organic layers washed with 10% K2CO3 (2×370 mL), and brine (2×370 mL), then dried over Na2SO4, and evaporated. The crude material was purified by flash chromatography, eluting with 0-29% EtOAc in hexanes. This afforded 26.3 g (81%) of (S)-tert-butyl 2,2-dimethyl-4-(3-((R)-4-methyl-2-oxooxazolidin-3-yl)-3-oxopropyl)oxazolidine-3-carboxylate as a clear syrup.

Workup

  1. stirringto stir for 13 hr
  2. temperaturewith concomitant warming to ambient temperature
  3. customthe mixture was transferred to a separatory funnel
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with EtOAc (3×370 mL)
  6. washthe combined organic layers washed with 10% K2CO3 (2×370 mL), and brine (2×370 mL)
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. customThe crude material was purified by flash chromatography
  10. washeluting with 0-29% EtOAc in hexanes

Sources & evidence

ORD record
ord-5aac55ebd9a8401db5d059ec07511c57
Source dataset
uspto-grants-2012_06
Patent number
US08198453B2

Reaction notes

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