Benzyl chloroformate → Tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxy-3-methoxyphenyl)propanoate

HRID 2410638Notes

Reaction equation

HRID 2410638 reaction equation
[NH2:1][CH:2]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([O:18][CH3:19])[CH:12]=1)[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[C:20](Cl)(=[O:29])[O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(Cl)Cl>[CH2:22]([O:21][C:20]([NH:1][CH:2]([CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([O:18][CH3:19])[CH:12]=1)[C:3]([O:5][C:6]([CH3:7])([CH3:9])[CH3:8])=[O:4])=[O:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

4

Reactant 2

HCID 10387Benzyl chloroformateHCID 58545613Tert-butyl 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoate

Product 1

HCID 58545693Tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxy-3-methoxyphenyl)propanoateYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedure 2: To a stirred solution of tert-butyl 2-amino-3-(4-hydroxy-3-methoxyphenyl)propanoate INT-1 (5.29 g, 19.8 mmol) and TEA (4.29 mL, 29.7 mmol) in DCM (50 mL) at 0° C. was treated with benzyl carbonochloridate (3.00 mL, 21.1 mmol) dropwise over 5 min. After stirring for 10 min, the mixture was washed with 1M HCl (150 mL), dried over MgSO4, and concentrated. The residue was taken up in MeOH (20 mL) and treated with 2 N NaOH (5 mL). After 10 min, the mixture was acidified and the product was purified by chromatography (EA/hexanes) to afford 4.7 g (59%) of tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxy-3-methoxyphenyl)propanoate INT-2. LCMS-ESI (m/z) calculated for C22H27NO6: 401. Found 424 [M+Na]+, tR=2.47 min (Method 6).

Workup

  1. customPrepared
  2. washthe mixture was washed with 1M HCl (150 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. additiontreated with 2 N NaOH (5 mL)
  6. waitAfter 10 min
  7. customthe product was purified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-69d21f8dc29e492cb2c64e9d5b7ba0c5
Source dataset
uspto-grants-2014_08
Patent number
US08816121B2

Reaction notes

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