Ammonium Chloride → HCID 70896147, compound

HRID 2403660Notes

Reaction equation

HRID 2403660 reaction equation
[C:1]12([N:6]3[C:29]4[CH:28]=[CH:27][C:11]5([CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]6[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=6)=[O:18])[CH2:13][CH2:12]5)[CH2:10][C:9]=4[CH:8]=[N:7]3)[CH2:5][CH:3]([CH2:4]1)[CH2:2]2.BrN1C(=[O:36])CCC1=O.C[N+]1([O-])CCOCC1.[Cl-].[NH4+]>C(OCC)(=O)C.C(#N)C.O1CCCC1.O.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC.[Zn]>[C:1]12([N:6]3[C:29]4[C:28](=[O:36])[CH2:27][C:11]5([CH2:12][CH2:13][N:14]([C:17]([O:19][CH2:20][C:21]6[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=6)=[O:18])[CH2:15][CH2:16]5)[CH2:10][C:9]=4[CH:8]=[N:7]3)[CH2:4][CH:3]([CH2:2]1)[CH2:5]2

Participants

11

Reactant 4

HCID 25517Ammonium ChlorideHCID 67184N-bromobutanimideHCID 82029Methyl morpholine oxideHCID 70896160HCID 70896160, compound

Product 1

HCID 70896147HCID 70896147, compoundYield 42%

Reagents, catalysts & solvents 6

HCID 23994ZincCatalystHCID 178419074HCID 178419074, compoundCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzyl 1-(bicyclo[1.1.1]pentan-1-yl)-1,4-dihydrospiro[indazole-5,4′-piperidine]-1′-carboxylate (340 mg, 0.87 mmol) in 3:1 tetrahydrofuran:water (10 mL) was added N-bromosuccinimide (155 mg, 0.87 mmol). The reaction was stirred at room temperature for 45 minutes. The reaction was diluted with ethyl acetate (50 mL), washed with 0.5 N aqueous sodium hydroxide (25 mL) and saturated aqueous sodium thiosulfate (25 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting oil was taken up in dichloromethane (5 mL) and treated with activated 4 A molecular sieves (500 mg) and tetrapropylammonium perruthenate (16 mg, 0.04 mmol). The slurry was treated with N-methylmorpholine-N-oxide (243 mg, 1.75 mmol) in acetonitrile (5 mL). The reaction was stirred at room temperature for 2 hours. The reaction was filtered through Celite and the filtrate was concentrated. The residue was purified by flash column chromatography (7-60% ethyl acetate/heptanes) to yield a clear oil. The oil was taken up in tetrahydrofuran (5 mL) and treated with saturated aqueous ammonium chloride (5 mL) and zinc dust (171 mg, 2.62 mmol). The mixture was stirred at room temperature for 30 minutes. The reaction was diluted with water (50 mL) and extracted with ethyl acetate (2×30 mL). The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography (7-60% ethyl acetate/heptanes) gave the title compound (148 mg, 42%) as a white solid. 1H NMR (400 MHz, CDCl3, δ): 7.34 (m, 6 H), 5.13 (s, 2 H), 3.51 (m, 4 H), 2.75 (s, 2 H), 2.59 (s, 1 H), 2.54 (s, 2 H), 2.41 (s, 6 H), 1.56 (m, 4 H).

Workup

  1. washwashed with 0.5 N aqueous sodium hydroxide (25 mL) and saturated aqueous sodium thiosulfate (25 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. stirringThe reaction was stirred at room temperature for 2 hours
  6. filtrationThe reaction was filtered through Celite
  7. concentrationthe filtrate was concentrated
  8. customThe residue was purified by flash column chromatography (7-60% ethyl acetate/heptanes)
  9. customto yield a clear oil
  10. stirringThe mixture was stirred at room temperature for 30 minutes
  11. extractionextracted with ethyl acetate (2×30 mL)
  12. washThe combined organics were washed with brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customPurification by flash column chromatography (7-60% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-4922b558f7704262852f87b8d0098fec
Source dataset
uspto-grants-2014_08
Patent number
US08802688B2

Reaction notes

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