Diisopropylethylamine → Methyl 2-[n-methyl-n-((r/s)-alpha-methyl-4-benzyloxyphenylacetyl)amino]-(r)-propionate

HRID 843393Notes

Reaction equation

HRID 843393 reaction equation
[CH3:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][CH:7]=1)[C:3]([OH:5])=O.[CH3:20][O:21][C:22](=[O:27])[C@@H:23]([CH3:26])[NH:24][CH3:25].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:25][N:24]([C@H:23]([CH3:26])[C:22]([O:21][CH3:20])=[O:27])[C:3](=[O:5])[CH:2]([C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][CH:7]=1)[CH3:1]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 13850986methyl (2R)-2-(methylamino)propanoateHCID 22464929HCID 22464929, compound

Product 1

HCID 69882983Methyl 2-[n-methyl-n-((r/s)-alpha-methyl-4-benzyloxyphenylacetyl)amino]-(r)-propionateYield 99%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R/S)-α-methyl-4-benzyloxyphenylacetic acid 45b (300 mg, 1.17 mmol) and N-methyl-D-alanine methyl ester (200 mg, 1.3 mmol) in DMF (5 mL) cooled in an ice bath was added BOP (531 mg, 1.2 mmol) followed by DIEA (0.7 mL, 4 mmol). The mixture was stirred at room temperature for 5 hours. EtOAc was added and the solution washed with NaHCO3, brine, citric acid and brine, dried (MgSO4), and concentrated. Purification on a silica gel column (40% EtOAc/hexane) gave the amide product (398 mg, 99%) as a solid. MS (CI—NH3): (M+H)+=356.

Workup

  1. washthe solution washed with NaHCO3, brine, citric acid and brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated
  4. customPurification on a silica gel column (40% EtOAc/hexane)

Sources & evidence

ORD record
ord-884ffbb0e36c4a7c83df5cec168f33f1
Source dataset
uspto-grants-2002_04
Patent number
US06376665B1

Reaction notes

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