Formic Acid → HCID 71116047, compound

HRID 1423852Notes

Reaction equation

HRID 1423852 reaction equation
[CH2:1]([C:3]1([CH2:19][NH:20][C:21]2[CH:22]=[C:23]([CH:26]=[CH:27][C:28]=2[N+:29]([O-])=O)[C:24]#[N:25])[CH2:18][CH2:17][CH2:16][C:5]2([O:9][C:8](=[O:10])[N:7]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:6]2)[CH2:4]1)[CH3:2].[CH:32](OC)(OC)OC.C(O)=O.C(O)(C(F)(F)F)=O>CO.CC#N.[Fe]>[CH2:1]([C:3]1([CH2:19][N:20]2[C:21]3[CH:22]=[C:23]([C:24]#[N:25])[CH:26]=[CH:27][C:28]=3[N:29]=[CH:32]2)[CH2:18][CH2:17][CH2:16][C:5]2([O:9][C:8](=[O:10])[N:7]([CH2:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:6]2)[CH2:4]1)[CH3:2]

Participants

8

Reactant 4

HCID 284Formic Acid2×HCID 6422Trifluoroacetic acidHCID 9005Trimethyl orthoformate2×HCID 71116054HCID 71116054, compound

Product 1

HCID 71116047HCID 71116047, compoundYield 116.5%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

To an orange solution containing 3-(((7-ethyl-3-neopentyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)amino)-4-nitrobenzonitrile (0.125 g, 0.292 mmol) in MeOH (2.48 mL) was added iron (325 mesh) (0.163 g, 2.92 mmol), trimethyl orthoformate (0.322 mL, 2.92 mmol), and formic acid (0.112 mL, 2.92 mmol). The reaction mixture was stirred at 65° C. for 21 h. Additional trimethyl orthoformate ((0.322 mL, 2.92 mmol) and formic acid (0.112 mL, 2.92 mmol) were added, and the reaction was stirred at 65° C. for another 4 h. The reaction was cooled to rt, diluted with MeCN (2 mL), and filtered through a Acrodisc CR 25 mm syringe filter with 0.2 μm PTFE membrane. The filtered solution was purified by reverse-phase HPLC (Sunfire Prep C18 column (30×150 mm); 15 min run; 25 mL/min elution; Solvent A: MeCN/0.1% TFA, Solvent B: water/0.1% TFA, gradient: 30-60% solvent A) to afford the title compound (0.139 g, 88% yield) as the TFA salt. 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H), 8.06 (d, J=8.53 Hz, 1H), 7.85 (s, 1H), 7.73 (dd, J=1.25, 8.53 Hz, 1H), 4.13 (s, 2H), 3.31 (dd, J=8.78, 22.84 Hz, 2H), 3.00 (dd, J=14.31, 38.15 Hz, 2H), 2.01 (d, J=13.55 Hz, 2H), 1.81-1.97 (m, 2H), 1.58-1.75 (m, 3H), 1.10-1.29 (m, 3H), 1.06 (t, J=7.40 Hz, 3H), 0.96 (s, 9H); MS (m/z) 409.2 (M+H+).

Workup

  1. stirringthe reaction was stirred at 65° C. for another 4 h
  2. temperatureThe reaction was cooled to rt
  3. filtrationfiltered through a Acrodisc CR 25 mm syringe
  4. filtrationfilter with 0.2 μm PTFE membrane
  5. customThe filtered solution was purified by reverse-phase HPLC (Sunfire Prep C18 column (30×150 mm); 15 min run; 25 mL/min elution; Solvent A: MeCN/0.1% TFA, Solvent B: water/0.1% TFA, gradient: 30-60% solvent A)

Sources & evidence

ORD record
ord-2dcc910a36d6463e983abd3dd2f74909
Source dataset
uspto-grants-2015_01
Patent number
US08927585B2

Reaction notes

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