Formaldehyde → HCID 16068423, compound

HRID 1256650Notes

Reaction equation

HRID 1256650 reaction equation
[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]23[CH2:17][CH:16]2[CH2:15][NH:14][CH2:13]3)=[CH:4][CH:3]=1.C=O.[C:20](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>>[CH3:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]23[CH2:17][CH:16]2[CH2:15][N:14]([CH3:20])[CH2:13]3)=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 16068422HCID 16068422, compound

Product 1

HCID 16068423HCID 16068423, compound

Procedure

A stirred solution/suspension of 1-(4-methylnaphthalen-1-yl)-3-azabicyclo[3.1.0]hexane (85 mg, 0.38 mmol) in 1,2-dichloromethane (12 mL) was treated with 37% aqueous formaldehyde (0.23 mL, 3.0 mmol), then with sodium triacetoxyborohydride (318 mg, 1.5 mmol), stirred for 3 h, then treated with 1N sodium hydroxide (5 mL). The organic layer was separated and the aqueous solution was extracted with methylene chloride containing 2-propanol (2×10 mL). The combined organic solution was dried (MgSO4) and concentrated in vacuo to afford 1-(4-methylnaphthalen-1-yl)-3-methyl-3-azabicyclo[3.1.0]hexane (76 mg, 84%, essentially pure without chromatography). This was dissolved in anhydrous ether (5 mL) and treated with 2N HCl/ether (0.35 mL, 0.7 mmol), stirred a few minutes, filtered, rinsed with ether, collected, and dried in vacuo to afford 1-(4-methylnaphthalen-1-yl)-3-methyl-3-azabicyclo[3.1.0]hexane, hydrochloride (72 mg, 82%) as a white solid. MS (M+1) 238.1. 1H NMR (CDCl3) 12.70 (br s, 1H), 8.16 (m, 1H), 8.04 (m, 1H), 7.58 (m, 2H), 7.37 (m, 1H), 7.26 (m, 1H), 4.20 (m, 1H), 4.06 (m, 1H), 3.50 (m, 1H), 3.14 (m, 1H), 2.90 (d, 3H, J=5 Hz), 2.68 (s, 3H), 2.40 (m, 1H), 2.13 (m, 1H), 1.22 (m, 1H). 13C NMR (CDCl3) δ 135.73, 133.21, 131.70, 126.81, 126.35, 126.33, 125.41, 124.54, 61.65, 57.62, 41.52, 30.97, 22.37, 19.75.

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous solution was extracted with methylene chloride
  3. additioncontaining 2-propanol (2×10 mL)
  4. dry with materialThe combined organic solution was dried (MgSO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cfcc84fa972b4bfdabb625699adbf7e0
Source dataset
uspto-grants-2013_06
Patent number
US08461196B2

Reaction notes

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