Triethylamine → Benzyl tert-butyl malonate

HRID 1616997Notes

Reaction equation

HRID 1616997 reaction equation
[C:1]([O:5][C:6](=[O:12])NCC(=O)N)([CH3:4])([CH3:3])[CH3:2].[CH2:13](N(CC)CC)C.Cl[C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22].C([O-])([O-])=O.[Na+].[Na+]>ClCCl.CN(C)C1C=CN=CC=1>[CH2:24]([O:23][C:21](=[O:22])[CH2:13][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:12])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 109100641,1-Dimethylethyl N-(2-amino-2-oxoethyl)carbamate

Product 1

HCID 2736712Benzyl tert-butyl malonateYield 95.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Carbamoylmethyl-carbamic acid tert-butyl ester (8a; 0.84 g, 4.8 mmol) was dissolved in dichloromethane (10 mL), and added with triethylamine (1.0 mL, 7.2 mmol) and benzyl chloroformate (0.85 g, 0.75 mL, 5.0 mmol) at 0° C. After stirring for 5 min, 4-dimethylaminopyridine (DMAP; 0.32 g, 2.6 mmol) was added slowly with continuous stirring at 0° C. for 1 h. After the reaction is completed, dichloromethane (10 mL) and saturated Na2CO3 solution (10 mL) were added. The organic phase was washed by H2O (10 mL), 1N HCl (20 mL), H2O (20 mL) and saturated NaCl solution (20 mL) separately, and dried over MgSO4 and concentrated under reduced pressure to remove dichloromethane to obtain white solid product 12 (1.15 g; 95%). 1H-NMR (200 MHz) (CDCl3) δ: 7.30˜7.38 (m, 5H, ArH), 5.17 (s, 2H, CO2CH2Ph), 5.02 (br, s, 1H, NHBOC), 3.94 (d, 2H, Gly-H), 1.43 [s, 9H, CO2C(CH3)3]

Workup

  1. stirringwith continuous stirring at 0° C. for 1 h
  2. washThe organic phase was washed by H2O (10 mL), 1N HCl (20 mL), H2O (20 mL) and saturated NaCl solution (20 mL) separately
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customto remove dichloromethane

Sources & evidence

ORD record
ord-9edbb5fd57f94745ba1d1c2d4ac135e7
Source dataset
uspto-grants-2014_07
Patent number
US08765934B2

Reaction notes

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