Glycine methyl ester hydrochloride → (2-Tert-butoxycarbonylamino-2-methylpropylamino)acetic acid methyl ester

HRID 1504940Notes

Reaction equation

HRID 1504940 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH2:6].[C:8]([O:12][C:13](=[O:20])[NH:14][C:15]([CH3:19])([CH3:18])[CH:16]=O)([CH3:11])([CH3:10])[CH3:9].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CCN(CC)CC>[CH3:2][O:3][C:4](=[O:7])[CH2:5][NH:6][CH2:19][C:15]([NH:14][C:13]([O:12][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:20])([CH3:16])[CH3:18]

Participants

7

Reactant 4

HCID 122755Glycine methyl ester hydrochlorideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 14578674tert-butyl N-(2-methyl-1-oxopropan-2-yl)carbamate2×

Product 1

HCID 86657631(2-Tert-butoxycarbonylamino-2-methylpropylamino)acetic acid methyl esterYield 65.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

Amino-acetic acid methyl ester hydrochloride (80.6 g) and Et3N (160 mL) were dissolved in DCM (1000 mL) and stirred for 15 min to liberate the amine from the salt. Then a solution of 1,1-dimethyl-2-oxo-ethyl)-carbamic acid tert-butyl ester (compound M; 29.0 g) in DCM (600 mL) was added. The resulting mixture was stirred for 0.5 hour at ambient temperature before NaBH(OAc)3 (102 g) was added and the mixture was stirred at ambient temperature overnight. Sat. aqueous NaHCO3 was added. The aqueous layer was extracted with DCM. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography to afford (2-tert-butoxycarbonylamino-2-methyl-propylamino)-acetic acid methyl ester (compound N; 26.5 g) as white solid which was used directly in the next step.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at ambient temperature overnight
  3. extractionThe aqueous layer was extracted with DCM
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-28e43c46441047899b877b15ff948821
Source dataset
uspto-grants-2015_12
Patent number
US09216961B2

Reaction notes

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