Formaldehyde → HCID 16068324, compound

HRID 332128Notes

Reaction equation

HRID 332128 reaction equation
[F: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+]>>[F: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 16068323HCID 16068323, compound

Product 1

HCID 16068324HCID 16068324, compound

Procedure

A stirred solution/suspension of 1-(4-fluoronaphthalen-1-yl)-3-azabicyclo[3.1.0]hexane (215 mg, 0.95 mmol) in 1,2-dichloromethane (12 mL) was treated with 37% aqueous formaldehyde (0.5 mL, 9.5 mmol), then with sodium triacetoxyborohydride (1.25 g, 4.75 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 a little 2-propanol (2×10 mL). The combined organic solution was dried (MgSO4) and concentrated in vacuo to afford 1-(4-fluoronaphthalen-1-yl)-3-methyl-3-azabicyclo[3.1.0]hexane (150 mg, 65%, 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 3-methyl-1-(4-fluoronaphthalen-1-yl)-3-aza-bicyclo[3.1.0]hexane, hydrochloride (150 mg, 82%) as a white solid. MS (M+1) 242.1. 1H NMR (DMSO-d6) δ 0.91-1.01 (m, 1 H) 2.01-2.09 (m, 1 H) 2.13-2.24 (m, 1 H) 2.72-2.84 (m, J=4.69 Hz, 3 H) 3.16-3.30 (m, 1 H) 3.72 (q, J=5.60 Hz, 2 H) 3.93 (dd, J=11.23, 5.17 Hz, 1 H) 7.31 (dd, J=10.74, 8.01 Hz, 1 H) 7.48-7.79 (m, 3 H) 8.07 (d, J=8.20 Hz, 1 H) 8.20 (d, J=8.40 Hz, 1 H). 13C (DMSO-d6) δ 14.51, 22.36, 29.97, 56.72, 60.47, 109.90, 121.34, 123.61, 125.04, 127.43, 128.50, 131.39, 134.24 157.08.

Workup

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

Sources & evidence

ORD record
ord-f1cc3d9ca1eb4e7fb74c4955c3151a24
Source dataset
uspto-grants-2014_11
Patent number
US08877798B2

Reaction notes

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