Diisopropylamine → HCID 18186696, compound

HRID 1357656Notes

Reaction equation

HRID 1357656 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([NH:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl:28][C:29]1[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[C:30]=1[CH2:31]Br>C1COCC1>[C:13]([NH:21][CH:22]([CH2:31][C:30]1[C:29]([Cl:28])=[CH:36][CH:35]=[CH:34][C:33]=1[Cl:37])[C:23]([O:25][CH2:26][CH3:27])=[O:24])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 301591-Bromomethyl-2,6-dichlorobenzeneHCID 226558Ethyl HippurateHCID 178418339Butyllithium

Product 1

HCID 18186696HCID 18186696, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution comprised of N,N-diisopropylamine (3.97 mL, 22.8 mmol) in dry THF (57 mL) was cooled to −78° C. under nitrogen and then solutions of n-butyl lithium in hexanes (14.25 mL, 22.8 mmol) and ethyl benzoylaminoacetate (2.37 g, 11.4 mmol) in dry THF (23 mL) were added dropwise sequentially. The mixture was stirred for 1 hour and then a solution comprised of 2,6-dichlorobenzyl bromide (1.87 g, 11.4 mmol) in dry TMF (2 mL) was added dropwise. The mixture was stirred for 1 hour at −78° C. and then for 30 minutes while allowing to warm. The mixture then was quenched with water (8 mL) and extracted with ethyl acetate (2×54 mL). The combined extracts were washed with 1M hydrochloric acid (1×27 mL) and saturated sodium chloride solution (1×27 mL), dried (Na2SO4) and concentrated on a rotary evaporator. Product was purified from the residue by flash column (silica gel, 10:90 to 50:50 v/v EtOAc-hexane) to provide crude ethyl 2-benzoylamino-3-(2,6-dichlorophenyl)propionate. The propionate ester was treated with lithium hydroxide (118.8 mg, 4.96 mmol) in ethanol (12 mL) and water (50 mL) for 15 hours. The mixture was then diluted with 1M hydrochloric acid (12 mL) and ethyl acetate (24 mL). The aqueous layer was separated and extracted with ethyl acetate (2×4 mL). The combined organic layers were washed with saturated sodium chloride solution (25 mL), dried (Na2SO4), filtered and concentrated on a rotary evaporator to provide 2-benzoylamino-3-(2,6-dichlorophenyl)propionic acid.

Workup

  1. additionwas added dropwise
  2. stirringThe mixture was stirred for 1 hour at −78° C.
  3. waitfor 30 minutes while allowing
  4. temperatureto warm
  5. customThe mixture then was quenched with water (8 mL)
  6. extractionextracted with ethyl acetate (2×54 mL)
  7. washThe combined extracts were washed with 1M hydrochloric acid (1×27 mL) and saturated sodium chloride solution (1×27 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated on a rotary evaporator
  10. customProduct was purified from the residue by flash column (silica gel, 10:90 to 50:50 v/v EtOAc-hexane)

Sources & evidence

ORD record
ord-ee79751d1f024d98b3194b3e452b6038
Source dataset
uspto-grants-2003_07
Patent number
US06593327B2

Reaction notes

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