Acetic Acid → ethyl 1-tert-butyl-7-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylate

HRID 45788Notes

Reaction equation

C([O:3][C:4]1[C:5](=O)[CH:6]([C:10](=O)[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:7][CH2:8][CH:9]=1)C.C(O)(=O)C.Cl.[C:23]([NH:27][NH2:28])([CH3:26])([CH3:25])[CH3:24]>C(O)C>[C:23]([N:27]1[C:5]2[C:4](=[O:3])[CH2:9][CH2:8][CH2:7][C:6]=2[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:28]1)([CH3:26])([CH3:25])[CH3:24]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of ethyl (3-ethoxy-2-oxocyclohex-3-en-1-yl)(oxo)acetate 10 g (42.6 mmol) and acetic acid 5 ml in absolute ethanol (150 ml) at room temperature was added tert-butyl hydrazine hydrochloride 6 g (48 mmol). The mixture was stirred at 60° C. for 3 hours. The volatiles were removed under vacuum, the residue was diluted with DCM and washed with sat. aqueous solution of NaHCO3, and with brine. The organic phase was dried with sodium sulfate, filtered, and concentrated. The crude material was purified by silica gel column chromatography eluting with ethyl acetate and hexane (1:2) to give ethyl 1-tert-butyl-7-oxo-4,5,6,7-tetrahydro-1H-indazole-3-carboxylate in 90% yield. LC/MS (254 nm) HPLC method 2 Rt 6.08 min. 1H NMR (400 MHz, DMSO-d6) δ ppm 4.18 (q, J=6.83 Hz, 2H) 2.93-2.30 (3 m, 6H) 1.58 (s, 9H), 1.16 (t, J=6.83 Hz, 3H). HRMS (ESI) calcd for C14H20N2O3 [M+H]+ 287.1366 found 287.1356.

Workup

customThe volatiles were removed under vacuum
additionthe residue was diluted with DCM
washwashed with sat. aqueous solution of NaHCO3
dry with materialThe organic phase was dried with sodium sulfate
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by silica gel column chromatography
washeluting with ethyl acetate and hexane (1:2)

Sources & evidence

ORD record: ord-935f9fdc11ca4b82b27ab25590c66746
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541576B2

Reaction notes

Loading…