Acetic Acid → (1S,2R,4S)-ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylate

HRID 1969845Notes

Reaction equation

HRID 1969845 reaction equation
[CH3:1][CH:2]1[CH2:6][C:5](=O)[CH2:4][CH:3]1[C:8]([O:10][CH2:11][CH3:12])=[O:9].CC(O)=O.[CH2:17]([NH:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH2:25]([N:24]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:5]1[CH2:4][CH:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH:2]([CH3:1])[CH2:6]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[CH2:25]([N:24]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@@H:5]1[CH2:4][C@H:3]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C@H:2]([CH3:1])[CH2:6]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 7656DibenzylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 13089479Ethyl 2-methyl-4-oxocyclopentanecarboxylate

Product 2

HCID 58010318Ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylateHCID 67216257(1S,2R,4S)-ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylateYield 150%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A round bottom flask was charged with ethyl 2-methyl-4-oxocyclopentanecarboxylate (10.0 g, 58.8 mmol) and DCE (180 mL). The solution was cooled to about 0° C. and AcOH (5.7 mL, 100 mmol) and dibenzylamine (11.3 mL, 58.8 mmol) were added dropwise, resulting in formation of a thick suspension. The reaction mixture was warmed to about 10° C. and sodium triacetoxyborohydride (21.2 g, 100 mmol) was added portionwise. The reaction mixture was stirred at ambient temperature for about 20 h then slowly poured into stirred saturated aqueous NaHCO3 (300 mL) and stirred for about 20 min. The layers were separated and the aqueous phase was extracted with DCM (3×100 mL). The combined organic extracts were washed with brine (2×100 mL), dried over anhydrous Na2SO4, and concd under reduced pressure. The crude yellow oil was purified via silica gel chromatography eluting with a gradient of 0-30% EtOAc in heptane to give ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylate (scalemic mixture of diastereomers), predominantly (1S,2R,4S) ethyl 4-(dibenzylamino)-2-methylcyclopentanecarboxylate (15.5 g, 75%) as a colorless oil: 1H NMR (pyridine-d5) δ 7.53 (dd, J=0.9, 7.9 Hz, 4H), 7.43-7.35 (m, 4H), 7.33-7.25 (m, 2H), 4.22-4.06 (m, 2H), 3.79 (d, J=14.2 Hz, 2H), 3.70 (d, J=14.2 Hz, 2H), 3.34-3.22 (m, 1H), 2.76 (dd, J=7.9, 16.6 Hz, 1H), 2.25-2.13 (m, 1H), 2.09-1.94 (m, 2H), 1.88-1.79 (m, 1H), 1.52 (dd, J=10.5, 22.5 Hz, 1H), 1.16 (t, J=7.1 Hz, 3H), 0.98 (d, J=7.0 Hz, 3H).

Workup

  1. customresulting in formation of a thick suspension
  2. temperatureThe reaction mixture was warmed to about 10° C.
  3. additionthen slowly poured
  4. stirringstirred for about 20 min
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted with DCM (3×100 mL)
  7. washThe combined organic extracts were washed with brine (2×100 mL)
  8. dry with materialdried over anhydrous Na2SO4, and concd under reduced pressure
  9. customThe crude yellow oil was purified via silica gel chromatography
  10. washeluting with a gradient of 0-30% EtOAc in heptane

Sources & evidence

ORD record
ord-a0e7db8df92e4d4aa2edb58c76b3cf5a
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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