Triethylamine → 4-((1R)-1-{[(tert-butylamino)carbonyl]amino}ethyl)-N-hydroxybenzamide

To the vial containing (R)-4-(1-aminoethyl)benzoic acid hydrochloride was added tert-butyl isocyanate (0.023 mL, 0.198 mmol), N,N dimethylformamide (3.0 mL), and triethylamine (0.22 mL, 1.59 mmol). After the reaction was stirred at rt for 16 h, HATU (0.075 g, 0.198 mmol) in N,N-dimethylformamide (0.5 mL) was added, immediately followed by the addition of O-(tert-butyldimethylsilyl)hydroxylamine (0.044 g, 0.30 mmol) in DCM (1 mL). This mixture was shaken at rt for 1 hr, after which the mixture was evaporated to dryness. To the residue was added hydrochloric acid (4 mL, 1% in IPA). After shaking at rt for 30 min, solid NaHCO3 was added to quench the excess acid, and the mixture was evaporated to dryness to give a solid residue. This solid was dissolved in DMSO (1.2 mL), and filtered; then purified via Gilson prep-HPLC [15-38% MeCN—H2O] to give the title compound (0.026 g, 47%) as a white solid. LC-MS: (FA) ES+ 280; 1H NMR (Methanol-d4, 400 MHz) 87.69 (d, J=8.3 Hz, 2H), 7.37 (d, J=8.3 Hz, 2H), 4.80 (q, J=7.0 Hz, 1H), 1.37 (d, J=7.0 Hz, 3H), 1.26 (s, 9H).

1. stirringThis mixture was shaken at rt for 1 hr
2. customafter which the mixture was evaporated to dryness
3. additionTo the residue was added hydrochloric acid (4 mL, 1% in IPA)
4. stirringAfter shaking at rt for 30 min
5. additionsolid NaHCO3 was added
6. customto quench the excess acid
7. customthe mixture was evaporated to dryness
8. customto give a solid residue
9. filtrationfiltered
10. customthen purified via Gilson prep-HPLC [15-38% MeCN—H2O]

ORD record

ord-c653dd13d4e54a5bbd44abe42bb7ca9a

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382197B2