Lithium hydroxide, monohydrate → 3-(Tert-butoxycarbonylamino)-2-(4-chloro-3-fluorobenzyl)propanoic acid

HRID 82361Notes

Reaction equation

HRID 82361 reaction equation
O[Li].O.[C:4]([O:8][C:9]([NH:11][CH2:12][CH:13]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([F:27])[CH:21]=1)[C:14]([O:16]CC)=[O:15])=[O:10])([CH3:7])([CH3:6])[CH3:5]>O.C1COCC1.CO>[C:4]([O:8][C:9]([NH:11][CH2:12][CH:13]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([F:27])[CH:21]=1)[C:14]([OH:16])=[O:15])=[O:10])([CH3:7])([CH3:5])[CH3:6]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 67338495Ethyl 3-(tert-butoxycarbonylamino)-2-(4-chloro-3-fluorobenzyl)propanoate

Product 1

HCID 673397543-(Tert-butoxycarbonylamino)-2-(4-chloro-3-fluorobenzyl)propanoic acidYield 100.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of Boc2O (1.3 g, 6.1 mmol) and ethyl 3-amino-2-(4-chloro-3-fluorobenzyl)propanoate (1.6 g, 6.1 mmol) in DCM (10 mL) was stirred overnight. The mixture was concentrated in vacuo and chromatographed (SiO2) using DCM as eluent to give ethyl 3-(tert-butoxycarbonylamino)-2-(4-chloro-3-fluorobenzyl)propanoate. LiOH—H2O (0.26 g, 6.1 mmol) in H2O (7 mL) was added to a solution of ethyl 3-(tert-butoxycarbonylamino)-2-(4-chloro-3-fluorobenzyl)propanoate (0.55 g, 1.5 mmol) in THF/MeOH (7/7 mL) and stirred overnight. The mixture was concentrated in vacuo, acidified to a pH of 1 with 1.0N HCl, and extracted with DCM. The DCM extracts were dried (Na2SO4), filtered, and concentrated in vacuo. The crude material was chromatographed (SiO2) using 10% MeOH/DCM as eluent to give 3-(tert-butoxycarbonylamino)-2-(4-chloro-3-fluorobenzyl)propanoic acid (0.5 g). LCMS (APCI+) [M-Boc+H]+232.0; Rf: 2.09 min.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. extractionextracted with DCM
  3. dry with materialThe DCM extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was chromatographed (SiO2)

Sources & evidence

ORD record
ord-f853aca0053d4690a55d14a298c48627
Source dataset
uspto-grants-2014_09
Patent number
US08846681B2

Reaction notes

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