HCID 53893969, compound → HCID 178451179, compound

HRID 1490019Notes

Reaction equation

HRID 1490019 reaction equation
C([Li])CCC.[CH2:6]([C@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]#[CH:22])=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)[CH2:7][CH3:8].Br[C:24]1[CH:29]=[CH:28][C:27]([CH:30]2[O:34][C@@H:33]([C:35]([O:37][CH2:38][CH2:39][CH2:40][CH3:41])=[O:36])[C@H:32]([C:42]([O:44][CH2:45][CH2:46][CH2:47][CH3:48])=[O:43])[O:31]2)=[CH:26][CH:25]=1>CCCCCC.O1CCCC1.CCOCC.[Cl-].[Zn+2].[Cl-].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH2:6]([C@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]2[CH:16]=[CH:17][C:18]([C:21]#[C:22][C:24]3[CH:29]=[CH:28][C:27]([CH:30]4[O:34][C@@H:33]([C:35]([O:37][CH2:38][CH2:39][CH2:40][CH3:41])=[O:36])[C@H:32]([C:42]([O:44][CH2:45][CH2:46][CH2:47][CH3:48])=[O:43])[O:31]4)=[CH:26][CH:25]=3)=[CH:19][CH:20]=2)[CH2:11][CH2:10]1)[CH2:7][CH3:8]

Participants

9

Reactant 3

HCID 53893969HCID 53893969, compoundHCID 178418339ButyllithiumHCID 178436317HCID 178436317, compound

Product 1

HCID 178451179HCID 178451179, compoundYield 18.1%

Reagents, catalysts & solvents 5

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
60 °C

Procedure

1.45 ml of an about 1.6M butyllithium solution in hexane were added dropwise at -50° C. to a solution of 0.5 g of 4-(trans-4-propylcyclohexyl)phenylacetylene in 5 ml of dry tetrahydrofuran and the mixture was left to react at this temperature for 30 min. Then, 4.4 ml of a 1M zinc chloride solution in ether were added dropwise, the cooling bath was removed and the mixture was left to react for 30 minutes. Thereupon, the mixture was cooled to 0° C. and at this temperature a solution of 0.95 g of dibutyl (4R,5R)-2-(4-bromophenyl)-1,3-dioxolane-4,5-dicarboxylate in 5 ml of dry tetrahydrofuran was added dropwise and thereafter 0.128 g of tetrakis(triphenylphosphine) palladium(0) was added. The reaction mixture was then heated to 60° C. for 15 hours., then cooled, partitioned between water and ether and the organic phase was separated and dried over magnesium sulfate. Thereupon, it was filtered over Celite, the solvent was evaporated and the residue was chromatographed on 100 g of silica gel with 5% ethyl acetate in cyclohexane. Further purification with active charcoal in isopropanol and two-fold crystallization from isopropanol gave 0.23 g of dibutyl (4R,5R)-2-{4-[4-(trans-4-propylcyclohexyl)phenylethynyl]phenyl}-1,3-dioxolane-4,5-dicarboxylate, m.p. (K-N*) 74.9° C., cl.p. (N*-I) 78.3° C.

Workup

  1. waitthe mixture was left
  2. customto react at this temperature for 30 min
  3. customthe cooling bath was removed
  4. waitthe mixture was left
  5. customto react for 30 minutes
  6. additionwas added dropwise
  7. temperature, then cooled
  8. custompartitioned between water and ether
  9. customthe organic phase was separated
  10. dry with materialdried over magnesium sulfate
  11. filtrationThereupon, it was filtered over Celite
  12. customthe solvent was evaporated
  13. customthe residue was chromatographed on 100 g of silica gel with 5% ethyl acetate in cyclohexane
  14. customFurther purification
  15. customwith active charcoal in isopropanol and two-fold crystallization from isopropanol

Sources & evidence

ORD record
ord-3854bdf8937047859ec39959e43e39ff
Source dataset
uspto-grants-1997_10
Patent number
US05681504

Reaction notes

Loading…