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tert-Butanol → (1S,2R)-ethyl 2-methyl-4-oxocyclopentanecarboxylate

HRID 1969844
Notes
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Reaction equation

HRID 1969844 reaction equation
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+].[CH3:53][C:54]1[CH:55]([C:60]([O:62][CH2:63][CH3:64])=[O:61])[CH2:56][C:57](=[O:59])[CH:58]=1.C(O)(C)(C)C>C1(C)C=CC=CC=1.[Cu]Cl>[CH3:53][CH:54]1[CH2:58][C:57](=[O:59])[CH2:56][CH:55]1[C:60]([O:62][CH2:63][CH3:64])=[O:61].[CH3:53][C@@H:54]1[CH2:58][C:57](=[O:59])[CH2:56][C@@H:55]1[C:60]([O:62][CH2:63][CH3:64])=[O:61]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 6386tert-ButanolHCID 634876Binap, (A+-)-HCID 11332690Ethyl 2-methyl-4-oxocyclopent-2-ene-1-carboxylateHCID 23676156Sodium t-butoxide

Product 2

HCID 13089479Ethyl 2-methyl-4-oxocyclopentanecarboxylateHCID 13089480
(1S,2R)-ethyl 2-methyl-4-oxocyclopentanecarboxylate
Yield 88.3%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 1140TolueneSolvent2×

Procedure

In a 1 L round-bottomed flask jacketed flask, copper(I) chloride (0.736 g, 7.43 mmol), (S)-(−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (4.63 g, 7.43 mmol), and sodium tert-butoxide (0.714 g, 7.43 mmol) in toluene (250 mL) were added to give a yellow solution. The mixture was stirred at ambient temperature for about 15 min. after which the solution became brown. The solution was cooled to about 5° C. and polymethylhydrosiloxane (14.86 mL, 223 mmol) was added and the solution was stirred at about 5° C. for about 40 min. The solution was cooled to about −15° C. and a solution of ethyl 2-methyl-4-oxocyclopent-2-enecarboxylate (25.00 g, 149 mmol) and tert-butyl alcohol (61.7 mL, 654 mmol) in toluene (250 mL) was added in one portion. The reaction stirred at −15° C. for 144 h. The reaction mixture was quenched by the addition of 1:1 ethanol/toluene (350 mL) and Celite® 545 (25 g). The mixture was stirred and allowed to warm to ambient temperature. The reaction mixture was concd in vacuo, chasing with heptane. Heptane (350 mL) was added to the residue and solids were removed by filtration. The filtrate was concd in vacuo and the crude product was purified by silica gel chromatography using a gradient of 10 to 50% EtOAc in heptane over 7 column volumes to give ethyl 2-methyl-4-oxocyclopentanecarboxylate (scalemic mixture of diastereomers), predominantly (1S,2R)-ethyl 2-methyl-4-oxocyclopentanecarboxylate (11.2 g, 42% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 4.19 (qd, J=7.1, 0.6, 2H), 3.17 (ddd, J=8.1, 6.8, 5.6, 1H), 2.76-2.56 (m, 2H), 2.67-2.46 (m, 2H), 2.43-2.29 (m, 2H), 2.16 (ddd, J=18.3, 7.8, 1.7, 1H), 1.29 (t, J=7.2, 3H), 1.06 (d, J=7.0, 3H).

Workup

  1. customIn a 1 L round-bottomed flask jacketed
  2. customto give a yellow solution
  3. temperatureThe solution was cooled to about 5° C.
  4. stirringthe solution was stirred at about 5° C. for about 40 min
  5. temperatureThe solution was cooled to about −15° C.
  6. stirringThe reaction stirred at −15° C. for 144 h
  7. customThe reaction mixture was quenched by the addition of 1:1 ethanol/toluene (350 mL) and Celite® 545 (25 g)
  8. stirringThe mixture was stirred
  9. temperatureto warm to ambient temperature
  10. additionHeptane (350 mL) was added to the residue and solids
  11. customwere removed by filtration
  12. customthe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-bd73c26765bc4ca4a1779ff42515d86e
Source dataset
uspto-grants-2013_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08426411B2

Reaction notes

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