Acetic Acid → 2-tert-Butoxycarbonylamino-3-(4-fluoro-phenylamino)-2-methyl-propionic acid methyl ester

HRID 491761Notes

Reaction equation

HRID 491761 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])([CH3:7])[CH:5]=O.[F:17][C:18]1[CH:24]=[CH:23][C:21]([NH2:22])=[CH:20][CH:19]=1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH3:1][O:2][C:3](=[O:16])[C:4]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])([CH3:7])[CH2:5][NH:22][C:21]1[CH:23]=[CH:24][C:18]([F:17])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 97314-FluoroanilineHCID 5003444Sodium cyanoborohydrideHCID 22630101Methyl 2-[(tert-butoxycarbonyl)amino]-2-methyl-3-oxopropanoate

Product 1

HCID 576789232-tert-Butoxycarbonylamino-3-(4-fluoro-phenylamino)-2-methyl-propionic acid methyl esterYield 53.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of 2-tert-butoxycarbonylamino-2-methyl-3-oxo-propionic acid methyl ester (2.35 g, 6.71 mmol) in methanol (25 mL) was added 4-fluoroaniline (0.53 mL, 5.59 mmol) and acetic acid (0.16 mL, 2.80 mmol). A solution of sodium cyanoborohydride (188 mg, 2.99 mmol) in methanol (25 mL) was added dropwise and the reaction mixture stirred for 3 hours at room temperature post addition. The solvent was removed in vacuo and the residue dissolved in DCM (50 mL). The organic solution was treated with aqueous sodium carbonate solution (20 mL, 1N), stirred for 20 min, and the aqueous layer removed. Concentration of the organic layer followed by purification of the residue using flash chromatography (SiO2, DCM) afforded the title compound as a yellow oil (970 mg, 53%).

Workup

  1. additionpost addition
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue dissolved in DCM (50 mL)
  4. additionThe organic solution was treated with aqueous sodium carbonate solution (20 mL, 1N)
  5. stirringstirred for 20 min
  6. customthe aqueous layer removed
  7. customConcentration of the organic layer followed by purification of the residue

Sources & evidence

ORD record
ord-d3602da0734447b5b59800747451b449
Source dataset
uspto-grants-2009_05
Patent number
US07531565B2

Reaction notes

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