Propionic Acid → HCID 78028916, compound

HRID 1423845Notes

Reaction equation

HRID 1423845 reaction equation
[CH3:1][C:2]1([CH2:18][NH:19][C:20]2[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=2[N+:28]([O-])=O)[C:23]#[N:24])[CH2:17][CH2:16][CH2:15][C:4]2([O:8][C:7](=[O:9])[N:6]([CH2:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:5]2)[CH2:3]1.[C:31](OC)(OC)(OC)[CH2:32][CH3:33].C(O)(=O)CC.C(O)(C(F)(F)F)=O>C(O)CC.CC#N.[Fe]>[CH2:32]([C:33]1[N:19]([CH2:18][C:2]2([CH3:1])[CH2:17][CH2:16][CH2:15][C:4]3([O:8][C:7](=[O:9])[N:6]([CH2:10][C:11]([CH3:12])([CH3:13])[CH3:14])[CH2:5]3)[CH2:3]2)[C:20]2[CH:21]=[C:22]([C:23]#[N:24])[CH:25]=[CH:26][C:27]=2[N:28]=1)[CH3:31]

Participants

8

Reactant 4

HCID 1032Propionic AcidHCID 6422Trifluoroacetic acidHCID 1411451,1,1-TrimethoxypropaneHCID 71116052HCID 71116052, compound

Product 1

HCID 78028916HCID 78028916, compoundYield 90.3%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 10311-PropanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

To an orange solution containing 3-(((7-methyl-3-neopentyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)amino)-4-nitrobenzonitrile (0.100 g, 0.241 mmol) in 1-propanol (2.41 mL) was added iron (325 mesh) (0.135 g, 2.41 mmol), trimethyl orthopropionate (0.324 g, 2.41 mmol), and propionic acid (0.179 g, 2.41 mmol). The reaction mixture was stirred at 65° C. for 2 h and then cooled to rt. The reaction was diluted with MeCN (2 mL) and filtered through an Acrodisc CR 25 mm syringe filter with a 0.2 μm PTFE membrane. The filtered solution was purified by reverse-phase HPLC (Sunfire Prep C18 (30×150 mm); Solvent A: MeCN/0.1% TFA, Solvent B: water/0.1% TFA; gradient: 25-55% solvent A over 15 min; 25 mL/min elution; 220 nm detection) to afford the title compound (0.092 g, 69% yield) as the TFA salt. 1H NMR (400 MHz, CDCl3) δ 8.07 (br. s., 1H), 7.83 (s, 1H), 7.69-7.79 (m, 1H), 4.08 (s, 2H), 3.32 (dd, J=8.78, 35.39 Hz, 2H), 3.01 (dd, J=14.05, 43.42 Hz, 2H), 2.05 (d, J=13.55 Hz, 1H), 1.85-1.99 (m, J=12.55 Hz, 2H), 1.48-1.77 (m, 5H), 1.20-1.44 (m, 8H), 0.96 (s, 9H). MS (m/z) 423.3 (M+H+).

Workup

  1. temperaturecooled to rt
  2. filtrationfiltered through an Acrodisc CR 25 mm syringe
  3. filtrationfilter with a 0.2 μm PTFE membrane
  4. customThe filtered solution was purified by reverse-phase HPLC (Sunfire Prep C18 (30×150 mm); Solvent A: MeCN/0.1% TFA, Solvent B: water/0.1% TFA; gradient: 25-55% solvent A over 15 min; 25 mL/min elution; 220 nm detection)

Sources & evidence

ORD record
ord-0f9afb1bca8046bbbaa4bf6dec95b580
Source dataset
uspto-grants-2015_01
Patent number
US08927585B2

Reaction notes

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