Ammonium Chloride → Ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate

HRID 1969604Notes

Reaction equation

HRID 1969604 reaction equation
[CH2:1]([CH:3]1[CH2:7][C:6](=[O:8])[CH2:5][CH:4]1[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH3:2].[BH4-].[Na+].[NH4+].[Cl-]>CO>[CH2:1]([CH:3]1[CH2:7][CH:6]([OH:8])[CH2:5][CH:4]1[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH3:2].[CH2:1]([C@@H:3]1[CH2:7][C@H:6]([OH:8])[CH2:5][C@@H:4]1[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH3:2].[CH2:1]([C@H:3]1[CH2:7][C@@H:6]([OH:8])[CH2:5][C@H:4]1[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH3:2]

Participants

7

Reactant 3

HCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 58010012Cyclopentanecarboxylic acid, 2-ethyl-4-oxo-, ethyl ester

Product 3

HCID 58557073Ethyl 2-ethyl-4-hydroxycyclopentanecarboxylateHCID 58557647HCID 58557647, compoundHCID 86660437(1R,2S,4R)-ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To ethyl 2-ethyl-4-oxocyclopentanecarboxylate (10 g, 54.3 mmol, Example #8, Step G) in MeOH (143 mL) was added NaBH4 (2.57 g, 67.8 mmol) portionwise. The resulting suspension was stirred for about 16 h at ambient temperature then saturated aqueous NH4Cl (240 mL) was added. The reaction mixture was stirred for about 20 min then the solution was partitioned with Et2O (300 mL). The organic layer was separated and the aqueous layer was washed with Et2O (2×150 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous MgSO4, filtered, and concd under reduced pressure. The product was purified by silica gel chromatography (220 g) eluting with a gradient of 30-70% EtOAc in heptane to give ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate (8.51 g, 84%, predominantly (1S,2R,4S)-ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate and (1R,2S,4R)-ethyl 2-ethyl-4-hydroxycyclopentanecarboxylate) as a clear oil: LC/MS (Table 1, Method b) Rt=2.02 min; MS m/z: 187 (M+H)+.

Workup

  1. stirringThe reaction mixture was stirred for about 20 min
  2. customthe solution was partitioned with Et2O (300 mL)
  3. customThe organic layer was separated
  4. washthe aqueous layer was washed with Et2O (2×150 mL)
  5. washThe combined organic layers were washed with brine (100 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. customThe product was purified by silica gel chromatography (220 g)
  9. washeluting with a gradient of 30-70% EtOAc in heptane

Sources & evidence

ORD record
ord-1fbb7d98332e4e67aa121a664fc5859f
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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