Formic Acid → HCID 71116062, compound

HRID 1423843Notes

Reaction equation

HRID 1423843 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:27]([O-])=O)=[C:6]([NH:8][CH2:9][C:10]2([CH3:26])[CH2:25][CH2:24][CH2:23][C:12]3([O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:13]3)[CH2:11]2)[CH:7]=1.[CH:30](O)=O.C(OC)(OC)OC>CO.[Fe]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:27]=[CH:30][N:8]([CH2:9][C:10]3([CH3:26])[CH2:25][CH2:24][CH2:23][C:12]4([O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:13]4)[CH2:11]3)[C:6]=2[CH:7]=1

Participants

6

Reactant 3

HCID 284Formic AcidHCID 9005Trimethyl orthoformateHCID 71116084HCID 71116084, compound

Product 1

HCID 71116062HCID 71116062, compound

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A solution containing 7-(((5-chloro-2-nitrophenyl)amino)methyl)-7-methyl-3-neopentyl-1-oxa-3-azaspiro[4.5]decan-2-one (0.100 g, 0.236 mmol) in MeOH (5 mL) was treated with iron (325 mesh) (0.132 g, 2.36 mmol) followed by formic acid (0.090 mL, 2.359 mmol) and trimethyl orthoformate (0.261 mL, 2.359 mmol). The resulting mixture was heated at 65° C. for 18 h. LCMS indicated partial conversion to desired product. Additional iron (0.100 g, 1.79 mmol), formic acid (0.200 mL, 5.22 mmol), and trimethyl orthoformate (0.500 mL, 4.53 mmol) were added, and the reaction was stirred at 80° C. for 3 h. The reaction was cooled to rt and filtered through filter paper. The collected solids were washed with MeOH, and the combined MeOH washings and filtrate were concentrated. The crude product was purified by reverse-phase HPLC (Sunfire Prep C18 column (30×150 mm); 14 minute run; 40 mL/min flow rate with at-column dilution; Solvent A: MeCN/0.1% TFA, Solvent B: water/0.1 TFA, gradient: 10-90% solvent A) to afford the title compound (0.071 g, 52% yield) as the TFA salt. 1H NMR (400 MHz, CDCl3) δ 8.88 (br. s., 1H), 7.89 (d, J=8.78 Hz, 1H), 7.56 (d, J=1.51 Hz, 1H), 7.49 (dd, J=1.63, 8.66 Hz, 1H), 7.27 (s, 1H), 4.08 (s, 2H), 3.26-3.40 (m, 1H), 3.06 (d, J=14.05 Hz, 1H), 2.92 (d, J=14.05 Hz, 1H), 2.05 (br. s., 1H), 1.79-1.99 (m, 2H), 1.69 (d, J=14.05 Hz, 1H), 1.58 (br. s., 1H), 1.42 (d, J=13.80 Hz, 1H), 1.28-1.37 (m, 2H), 1.27 (s, 3H), 0.95 (s, 9H). MS (m/z) 404.2 (M+H+).

Sources & evidence

ORD record
ord-810eb963bfb543f985b5e7806b5f9684
Source dataset
uspto-grants-2015_01
Patent number
US08927585B2

Reaction notes

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