Formaldehyde → 9-(3,4-Dichloro-phenyl)-3-methyl-3-aza-spiro[5.5]undec-8-ene

HRID 419281Notes

Reaction equation

HRID 419281 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:19][CH2:18][C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].C=O.[C:22](O[BH-](OC(=O)C)OC(=O)C)(=[O:24])C.[Na+].ClCCl.CO>ClC(Cl)C.CO>[OH-:24].[NH4+:15].[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH2:19][CH2:18][C:12]3([CH2:13][CH2:14][N:15]([CH3:22])[CH2:16][CH2:17]3)[CH2:11][CH:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

8

Reactant 4

HCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 160063269-(3,4-Dichlorophenyl)-3-azaspiro[5.5]undec-8-eneHCID 21226129Dichloromethane methanol

Product 2

HCID 14923Ammonium HydroxideYield 1%HCID 160064359-(3,4-Dichloro-phenyl)-3-methyl-3-aza-spiro[5.5]undec-8-eneYield 105.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

To an ice cooled solution of 9-(3,4-dichloro-phenyl)-3-aza-spiro[5.5]undec-8-ene (410 mg, 1.38 mmol) in dichloroethane (12 mL) and methanol (4 mL), formaldehyde (37% in water, 157 μL, 2.08 mmol) was added and stirred for 1 h at 0° C. Sodium triacetoxy-borohydride (585 mg, 2.76 mmol) was added and the mixture stirred at room temperature over night. The reaction was quenched with aqueous sodium hydrogen-carbonate and evaporated. The remaining aqueous phase was extracted four times with dichloromethane and the combined organic phase was dried (sodium sulfate), filtered and evaporated to give 320 mg of crude material. Flash chromatography (dichloromethane/methanol 9:1 with 1% ammonium hydroxide) gave 225 mg (52%) of 9-(3,4-dichloro-phenyl)-3-methyl-3-aza-spiro[5.5]undec-8-ene as an yellow oil.

Workup

  1. stirringthe mixture stirred at room temperature over night
  2. customThe reaction was quenched with aqueous sodium hydrogen-carbonate
  3. customevaporated
  4. extractionThe remaining aqueous phase was extracted four times with dichloromethane
  5. dry with materialthe combined organic phase was dried (sodium sulfate)
  6. filtrationfiltered
  7. customevaporated
  8. customto give 320 mg of crude material

Sources & evidence

ORD record
ord-1f3b281e26c54128b69c48a8d55c379b
Source dataset
uspto-grants-2012_01
Patent number
US08093388B2

Reaction notes

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