Hydrochloric Acid → 3-(1-Carboxycyclopentyl)-2(dibenzylaminomethyl)propanoic acid t-butyl ester

HRID 1087976Notes

Reaction equation

HRID 1087976 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH:13]1([C:18]([OH:20])=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14]1.[C:21]([O:25][C:26](=[O:45])[C:27]([CH2:29][N:30]([CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[CH2:28])([CH3:24])([CH3:23])[CH3:22].Cl>O1CCCC1>[C:21]([O:25][C:26](=[O:45])[CH:27]([CH2:29][N:30]([CH2:38][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH2:28][C:13]1([C:18]([OH:20])=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14]1)([CH3:22])([CH3:23])[CH3:24]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 18840Cyclopentanecarboxylic acidHCID 54200068Tert-butyl 2-[(dibenzylamino)methyl]prop-2-enoateHCID 178418339Butyllithium

Product 1

HCID 221554593-(1-Carboxycyclopentyl)-2(dibenzylaminomethyl)propanoic acid t-butyl esterYield 57.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

To a stirred solution of diisopropylamine (14.98 g, 20.75 ml, 148 mmole) in dry tetrahydrofuran (250 ml) cooled to -30° C. under nitrogen, was added dropwise, n-butyl lithium (59.3 ml of a 2.5M solution, 148 mmole), keeping the temperature below -20° C. The reaction was stirred at -20° C. for 1 hour, then cooled to -30° C. and cyclopentanecarboxylic acid (8.05 g, 7.65 ml, 70.6 mmole) added dropwise in a small amount of dry tetrahydrofuran. The reaction mixture was stirred at 0° C. for two hours, during which time a white precipitate formed. The solution was then cooled to -70° C., and a solution of 2-(dibenzylaminomethyl)-propenoic acid t-butyl ester (23.8 g, 70.6 mmol) in dry tetrahydrofuran (35 ml) was added dropwise. The reaction was left overnight (below -40° C.), and then poured into iced hydrochloric acid (4.2 eq, final pH=2) and the product extracted into diethyl ether. The ether layer was washed with hydrochloric acid, water (2×), dried (Na2SO4) and evaporated to yield the crude product (40 g). This was chromatographed over silica gel (500 g) eluting with dichloromethane containing methanol (0 to 5%) to yield, on evaporation of the pure fractions, 3-(1-carboxycyclopentyl)-2(dibenzylaminomethyl)propanoic acid t-butyl ester as an oil (18.3 g, 57%). Found: C,74 38; H,8.41; N,2 91. C28H37NO4 requires C,74.47; H,8.26; N,3.10%.

Workup

  1. additionwas added dropwise
  2. customthe temperature below -20° C
  3. temperaturecooled to -30° C.
  4. stirringThe reaction mixture was stirred at 0° C. for two hours, during which time a white precipitate
  5. customformed
  6. temperatureThe solution was then cooled to -70° C.
  7. waitThe reaction was left overnight (below -40° C.)
  8. extractionfinal pH=2) and the product extracted into diethyl ether
  9. washThe ether layer was washed with hydrochloric acid, water (2×)
  10. dry with materialdried (Na2SO4)
  11. customevaporated
  12. customto yield the crude product (40 g)
  13. customThis was chromatographed over silica gel (500 g)
  14. washeluting with dichloromethane
  15. additioncontaining methanol (0 to 5%)

Sources & evidence

ORD record
ord-d7bc0cd6185a4764ad998c826b692a62
Source dataset
uspto-grants-1990_10
Patent number
US04960792

Reaction notes

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