Pivaloyl chloride → HCID 69681756, compound

HRID 394926Notes

Reaction equation

HRID 394926 reaction equation
[CH3:1][C:2]1([CH3:23])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]2[CH:7]=[C:6]([CH:14]([CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[C:15](O)=[O:16])[CH:5]=[CH:4][C:3]1=2.CC(C)(C)C(Cl)=O.[Cl-].[Li+].[CH3:33][CH:34]([C@@H:36]1[C:40]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:39][C:38](=[O:53])[NH:37]1)[CH3:35]>C1COCC1.C(N(CC)CC)C>[CH3:35][CH:34]([C@@H:36]1[C:40]([C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:39][C:38](=[O:53])[N:37]1[C:15](=[O:16])[C@@H:14]([C:6]1[CH:5]=[CH:4][C:3]2[C:2]([CH3:23])([CH3:1])[CH2:11][CH2:10][C:9]([CH3:13])([CH3:12])[C:8]=2[CH:7]=1)[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH3:33]

Participants

7

Reactant 4

HCID 62493Pivaloyl chlorideHCID 433294Lithium ChlorideHCID 11300512(4R)-5,5-Diphenyl-4-(propan-2-yl)-1,3-oxazolidin-2-oneHCID 17949413HCID 17949413, compound

Product 1

HCID 69681756HCID 69681756, compoundYield 89.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
-30 °C

Procedure

2.0 g of (RS)-2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-heptanoic acid were dissolved in 30 ml of THF and cooled to −30° C. To the cooled mixture, were added successively, 2.3 ml of triethylamine and 780 μl of trimethylacetyl chloride. The mixture was kept at −30° C. for two hours. 308 mg of lithium chloride were added followed by 978 mg of (R)-4-(1-methylethyl)-5,5-diphenyloxazolidin-2-one (Hintermann T., Seebach D., Helv. Chim. Acta, 1998, 81, 2093). The mixture was allowed to warm to room temperature and was kept at that temperature for 18 hours. The reaction mixture was quenched by the addition of one portion of 30 ml of a saturated aqueous ammonium chloride solution. The resulting mixture was extracted with three portions of 30 ml of ether. The combined organic extracts were washed with two portions of 30 ml of 1N hydrochloric solution, one portion of 30 ml of water and one portion of 30 ml of saturated aqueous sodium chloride solution. The organic phase was dried over MgSO4 and the solvent evaporated. The residual yellow oil was purified by flash chromatography (SiO2, 3% ethyl acetate/hexanes to 20% ethyl acetate/hexanes, dry pack), yielding 1.8 g of the titled compound and 0.8 g of the starting acid, 1H NMR (CDCl3): 7.40-7.20 (m, 6H), 7.15-6.95 (m, 6H), 6.77 (dd, J=8.2, 2.0 Hz, 1H), 5.26 (d, J=3.4 Hz, 1H), 4.92 (dd, J=8.8, 6.2 Hz, 1H), 2.15 (m, 1H), 1.97 (m, 1H), 1.70 (m, 1H), 1.58 (br. s, 4H), 1.35-1.25 (m, 6H), 1.23 (s, 3H), 1.20 (s, 3H), 1.17 (s, 3H), 1.03 (s, 3H), 0.92 (d, J=7.0 Hz, 3H), 0.85 (t, J=6.8 Hz, 3H), 0.80 (d, J=6.8 Hz, 3H).

Workup

  1. additionTo the cooled mixture, were added successively
  2. temperatureto warm to room temperature
  3. waitwas kept at that temperature for 18 hours
  4. customThe reaction mixture was quenched by the addition of one portion of 30 ml of a saturated aqueous ammonium chloride solution
  5. extractionThe resulting mixture was extracted with three portions of 30 ml of ether
  6. washThe combined organic extracts were washed with two portions of 30 ml of 1N hydrochloric solution, one portion of 30 ml of water and one portion of 30 ml of saturated aqueous sodium chloride solution
  7. dry with materialThe organic phase was dried over MgSO4
  8. customthe solvent evaporated
  9. customThe residual yellow oil was purified by flash chromatography (SiO2, 3% ethyl acetate/hexanes to 20% ethyl acetate/hexanes, dry pack)

Sources & evidence

ORD record
ord-c85e3f65ac4245109597878e8e1d0e7e
Source dataset
uspto-grants-2003_08
Patent number
US06603012B2

Reaction notes

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