Diisopropylethylamine → methyl N-(tert-butoxycarbonyl)-3-(tetrahydro-2H-pyran-4-yl)-L-alanylglycinate

HRID 1972341Notes

Reaction equation

HRID 1972341 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([OH:19])=O)[CH2:10][CH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[CH3:45][O:46][C:47](=[O:50])[CH2:48][NH2:49].CCN(C(C)C)C(C)C>O.CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:17]([NH:49][CH2:48][C:47]([O:46][CH3:45])=[O:50])=[O:19])[CH2:10][CH:11]1[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 122755Glycine methyl ester hydrochlorideHCID 7168106(S)-2-((t-Butoxycarbonyl)amino)-3-(tetrahydro-2H-pyran-4-yl)propanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 66582350methyl N-(tert-butoxycarbonyl)-3-(tetrahydro-2H-pyran-4-yl)-L-alanylglycinateYield 76.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 100-mL round-bottomed flask was charged with N-(tert-butoxycarbonyl)-3-(tetrahydro-2H-pyran-4-yl)-L-alanine (3.11 g, 11.38 mmol), HATU (5.41 g, 14.22 mmol), glycine methyl ester hydrochloride (1.714 g, 13.65 mmol, Sigma-Aldrich, St. Louis, Mo.), and 10 mL of DMF. To this was added Hünig's base (4.37 mL, 25.03 mmol). After 30 min at room temperature, the mixture was diluted with water (100 mL) and extracted with EtOAc (2×200 mL). The layers were separated and the organic extracts were washed with water (2×100 mL) and brine (50 mL), dried (MgSO4), filtered and concentrated to give methyl N-(tert-butoxycarbonyl)-3-(tetrahydro-2H-pyran-4-yl)-L-alanylglycinate (3.00 g) as a yellow oil.

Workup

  1. extractionextracted with EtOAc (2×200 mL)
  2. customThe layers were separated
  3. washthe organic extracts were washed with water (2×100 mL) and brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-e5f7c2c0182f4757a78030fdb6ec1c2c
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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