1,2-Dichloroethane → HCID 68934896, compound

HRID 2277105Notes

Reaction equation

HRID 2277105 reaction equation
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]12[CH2:15][CH:14]1[CH2:13][NH:12][CH2:11]2.C=O.[C:18](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].[Cl:34]CCCl>>[ClH:34].[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[C:2]1[C:10]12[CH2:15][CH:14]1[CH2:13][N:12]([CH3:18])[CH2:11]2

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 25166638HCID 25166638, compound

Product 1

HCID 68934896HCID 68934896, compound

Procedure

A stirred solution of 1-(benzothiophen-2-yl)-3-azabicyclo[3.1.0]hexane (72 mg, 0.348 mmol) in 1,2-dichloroethane (7 ml) was treated with 37% formaldehyde (0.21 mL, 2.8 mmol), then with sodium triacetoxyborohydride (294.5 mg, 1.39 mmol) and this reaction mixture was stirred at room temperature for 3 h. 1N sodium hydroxide (7 mL) was then added, stirring continued for a few minutes, and the organic layer was separated. The aqueous layer was washed with methylene chloride, and the organic layers were combined, washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was chromatographed on a silica gel column (eluted with 90:9:1 methylene chloride/ethanol/ammonia). The oily 1-(benzothiophen-2-yl)-3-methyl-3-aza-bicyclo[3.1.0]hexane (71.6 mg, 90%) was converted to the hydrochloride salt by treating with 2N HCl/ether (49 mg, 53%). MS (M+1) 229.79. 1H NMR (MeOD-d4) δ 7.84-7.66 (m, 2H), 7.39-7.23 (m, 3H), 4.11-4.02 (m, 1H), 3.85-3.71 (m, 2H), 3.68-3.60 (m, 1H), 3.07-2.97 (s, 3H), 2.31-2.21 (m, 1H), 1.56-1.44 (m, 2H). 13C NMR (METHANOL-d4) δ 142.20, 140.06, 138.95, 124.56, 124.41, 123.18, 121.96, 121.92, 59.69, 57.19, 40.00, 27.81, 25.6, 16.21.

Workup

  1. waitcontinued for a few minutes
  2. customthe organic layer was separated
  3. washThe aqueous layer was washed with methylene chloride
  4. washwashed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was chromatographed on a silica gel column (eluted with 90:9:1 methylene chloride/ethanol/ammonia)
  9. additionby treating with 2N HCl/ether (49 mg, 53%)

Sources & evidence

ORD record
ord-18a742cf484f4789b9570e70d9966c32
Source dataset
uspto-grants-2015_09
Patent number
US09133159B2

Reaction notes

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