Hydrochloric Acid → HCID 22053942, compound

HRID 1830138Notes

Reaction equation

HRID 1830138 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([CH:20]1[CH2:24][O:23][C:22](=[O:25])[N:21]1[C:26](=[O:36])[CH2:27][CH2:28][CH2:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Br[CH2:38][C:39]([N:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1)=[O:40].Cl>C1COCC1.CCCCCC>[CH2:13]([CH:20]1[CH2:24][O:23][C:22](=[O:25])[N:21]1[C:26](=[O:36])[CH:27]([CH2:28][CH2:29][CH:30]1[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1)[CH2:38][C:39]([N:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1)=[O:40])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 139968762-Bromo-1-(morpholin-4-yl)ethan-1-oneHCID 22054083HCID 22054083, compoundHCID 178418339Butyllithium

Product 1

HCID 22053942HCID 22053942, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of diisopropylamine (1.92 mL, 13.68 mmol) in dry THF (50 mL) was cooled to −20° C. A 2.5M solution of n-butyl lithium in hexane (4.4 mL) was added with a syringe. The mixture was stirred for 30 min and then cooled to −78° C. A solution of 4-benzyl-3-(4-cyclohexyl-butyryl)-oxazolidin-2-one (3 g, 9.12 mmol) in THF (10 mL) was added slowly over 3 min. Stirring was continued for 30 min, then a solution of 2-Bromo-1-morpholin-4-yl-ethanone (2.28 g, 10.94 mmol) in THF (4 mL) was added over 3 min. The mixture was allowed to come to room temperature over 5 h. 1N HCl (50 mL) was added and the product was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with saturated aqueous NaHCO3 (200 mL) and brine (200 mL), dried with MgSO4 and evaporated under vacuum. The product (1-(4-benzyl-2-oxo-oxazolidin-3-yl)-2-(2-cyclohexyl-ethyl)-4-morpholin-4-yl-butane-1,4-dione) was obtained after purification by flash chromatography as a single diastereomer (2.5 g). 1H NMR: (CDCl3) 7.35–7.22(m, 5H), 4.69–4.62 (m, 1H), 4.28–4.10 (m, 3H), 3.76–3.46 (m, 8H), 3.37 (d, J=13.6 Hz, 1H), 2.91 (ddd, J=16.4 Hz, J=13 Hz, J=3 Hz, 1H), 2.76 (ddd, J=13.5 Hz, J=11 Hz, J=3 Hz, 1H), 2.51 (dt, J=13.6 Hz, J=3 Hz, 1H), 1.76–0.80 (m, 15H). MS: (M+H)+ 457.

Workup

  1. stirringStirring
  2. waitwas continued for 30 min
  3. waitto come to room temperature over 5 h
  4. extractionthe product was extracted with ethyl acetate (3×100 mL)
  5. washThe combined organic layers were washed with saturated aqueous NaHCO3 (200 mL) and brine (200 mL)
  6. dry with materialdried with MgSO4
  7. customevaporated under vacuum

Sources & evidence

ORD record
ord-56126bd0f3024c54a4d3248d4ac90ffa
Source dataset
uspto-grants-2006_06
Patent number
US07064123B1

Reaction notes

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