Dimethylformamide → (R)-tert-butyl 2-(3-cyclopentylureido)-2-phenylacetate

Reaction equation

Cl.[NH2:2][C@H:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:4]([OH:6])=[O:5].CCN([CH:19]([CH3:21])[CH3:20])C(C)C.[CH:22]1([N:27]=[C:28]=[O:29])[CH2:26][CH2:25][CH2:24][CH2:23]1.[CH3:30]N(C=O)C>>[CH:22]1([NH:27][C:28](=[O:29])[NH:2][C@H:3]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4]([O:6][C:19]([CH3:21])([CH3:30])[CH3:20])=[O:5])[CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

Reactant 4

HCID 6228Dimethylformamide

HCID 81531Diisopropylethylamine

HCID 643500Cyclopentyl Isocyanate

HCID 12238435(R)-2-Amino-2-phenylacetic acid hydrochloride

Product 1

HCID 59166526(R)-tert-butyl 2-(3-cyclopentylureido)-2-phenylacetate

Procedure

To a stirred solution of (R)-2-amino-2-phenylacetic acid hydrochloride (1.0 g, 4.10 mmol) and Hunig's base (1.0 mL, 6.15 mmol) in DMF (15 mL) was added cyclopentyl isocyanate (0.46 mL, 4.10 mmol) dropwise and over 10 minutes. After stirring at room temperature for 3 hours, the reaction was concentrated under reduced pressure and the resulting residue was traken up in ethyl acetate. The organic layer was washed with H2O and brine, dried (MgSO4), filtered, and concentrated under reduced pressure. (R)-tert-butyl 2-(3-cyclopentylureido)-2-phenylacetate was obtained as an opaque oil (1.32 g; 100%) and used without further purification. 1H NMR (500 MHz, CD3Cl-D) δ ppm 1.50-1.57 (m, 2H) 1.58-1.66 (m, 2H) 1.87-1.97 (m, 2H) 3.89-3.98 (m, 1H) 5.37 (s, 1H) 7.26-7.38 (m, 5H). LCMS: Anal. Calcd. for C18H26N2O3 318.19 found 319.21 (M+H)+; HPLC XTERRA C-18 3.0×50 mm, 0 to 100% B over 4 minutes, 1 minute hold time, A=90% water, 10% methanol, 0.1% TFA, B=10% water, 90% methanol, 0.1% TFA, RT=2.82 min, 96% homogeneity index.