Acetic Acid → Benzyl 1-tert-butyl-1,4-dihydrospiro[indazole-5,4'-piperidine]-1'-carboxylate

HRID 2403656Notes

Reaction equation

HRID 2403656 reaction equation
CN([CH:4]=[C:5]1[CH2:25][C:9]2([CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[CH2:11][CH2:10]2)[CH:8]=[CH:7][C:6]1=O)C.C(O)(=O)C.Cl.[C:32]([NH:36][NH2:37])([CH3:35])([CH3:34])[CH3:33]>C(O)C>[C:32]([N:36]1[C:6]2[CH:7]=[CH:8][C:9]3([CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)=[O:16])[CH2:13][CH2:14]3)[CH2:25][C:5]=2[CH:4]=[N:37]1)([CH3:35])([CH3:34])[CH3:33]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 81889tert-Butylhydrazine monohydrochlorideHCID 66835449Benzyl 10-((dimethylamino)methylene)-9-oxo-3-azaspiro[5,5]undec-7-ene-3-carboxylate

Product 1

HCID 58252496Benzyl 1-tert-butyl-1,4-dihydrospiro[indazole-5,4'-piperidine]-1'-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Benzyl 10-((dimethylamino)methylene)-9-oxo-3-azaspiro[5.5]undec-7-ene-3-carboxylate (59.2 g, 167 mmol) was dissolved in ethanol (835 mL). To the solution was added acetic acid (20 mL, 345 mmol) and tert-butylhydrazine hydrochloride (29.1 g, 234 mmol). The reaction was heated to reflux for 1 hour. The reaction was cooled to room temperature and concentrated to an orange oil. Purification by flash column chromatography (20-40% ethyl acetate/heptanes) afforded the title compound (50 g, 79%) as a pale yellow solid. +ESI (M+H) 380.5; 1H NMR (400 MHz, CDCl3, δ): 7.26-7.40 (m, 5 H), 7.17 (s, 1 H), 6.66 (d, J=9.95 Hz, 1 H), 5.77 (d, J=10.15 Hz, 1 H), 5.12 (s, 2 H), 3.38-3.64 (m, 4 H), 2.58 (s, 2 H), 1.60 (s, 12 H), 1.50 (br. s., 1 H).

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 1 hour
  3. concentrationconcentrated to an orange oil
  4. customPurification by flash column chromatography (20-40% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-80d79a81ad1548fb93aa0570028bcfc0
Source dataset
uspto-grants-2014_08
Patent number
US08802688B2

Reaction notes

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