Ammonium Chloride → (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoate

HRID 1913559Notes

Reaction equation

HRID 1913559 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:22]([O:24][CH3:25])=[O:23])[CH2:10][C:11]1[C:19]([CH3:20])=[CH:18][C:14]([C:15](O)=[O:16])=[CH:13][C:12]=1[CH3:21])=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C[N:29]([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[NH4+].[Cl-]>CN(C=O)C>[CH3:25][O:24][C:22](=[O:23])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:10][C:11]1[C:19]([CH3:20])=[CH:18][C:14]([C:15](=[O:16])[NH2:29])=[CH:13][C:12]=1[CH3:21]

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 58631279(S)-4-(2-tert-Butoxycarbonylamino-2-methoxycarbonylethyl)-3,5-dimethylbenzoic acid

Product 1

HCID 58631271(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(4-carbamoyl-2,6-dimethylphenyl)propanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a stirring solution of (S)-4-(2-tert-butoxycarbonylamino-2-methoxycarbonylethyl)-3,5-dimethylbenzoic acid (3.00 g, 8.54 mmol), PyBOP (6.68 g, 12.8 mmol) and HOBt (1.74 g, 12.8 mmol) in DMF (36 mL) was added DIPEA (5.96 mL, 34.2 mmol) and NH4Cl (0.92 g, 17.1 mmol). The resulting mixture was stirred at rt for 40 min before being partitioned between aqueous NH4Cl solution and EtOAc. The separated organic phase was washed sequentially with 2N citric acid aqueous solution, saturated aqueous NaHCO3 solution, and brine, then dried over Na2SO4 overnight. After filtration and concentration, the residue was purified by flash column chromatography (eluent: EtOAc) to give the product. (3.00 g, 100%); 1H NMR (300 MHz, CDCl3): δ 1.36 (9H, s), 2.39 (6H, s), 3.11 (2H, J=7.2 Hz), 3.65 (3H, s), 4.53-4.56 (1H, m), 5.12 (1H, d, J=8.7 Hz), 5.65 (1H, br s), 6.09 (1H, br s), 7.46 (2H, s); MS (ES+) (relative intensity): 250.9 (100) (M−Boc)+.

Workup

  1. custombefore being partitioned between aqueous NH4Cl solution and EtOAc
  2. washThe separated organic phase was washed sequentially with 2N citric acid aqueous solution, saturated aqueous NaHCO3 solution, and brine
  3. dry with materialdried over Na2SO4 overnight
  4. filtrationAfter filtration and concentration
  5. customthe residue was purified by flash column chromatography (eluent: EtOAc)
  6. customto give the product

Sources & evidence

ORD record
ord-5606e353b2154900a15969964d4826da
Source dataset
uspto-grants-2013_12
Patent number
US08609709B2

Reaction notes

Loading…