Dimethylamine → HCID 66781728, compound

HRID 1096717Notes

Reaction equation

HRID 1096717 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]23[CH2:14][CH:13]2[CH2:12][CH2:11][C:10]3=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:16][NH:17][CH3:18].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.Cl[Ti](Cl)(Cl)Cl>[ClH:1].[CH3:16][N:17]([CH3:18])[CH:10]1[CH2:11][CH2:12][CH:13]2[C:9]1([C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1)[CH2:14]2

Participants

6

Reactant 3

HCID 674DimethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 44138623HCID 44138623, compound

Product 1

HCID 66781728HCID 66781728, compoundYield 75.5%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 1-(3,4-dichlorophenyl)bicyclo[3.1.0]hexan-2-one (170 mg, 0.70 mmol) in dichloromethane (6 mL) was cooled to 0° C. and dimethylamine (2M solution in THF, 1.1 mL, 2.2 mmol) and TiCl4 (66 mg; 0.35 mmol; 0.5 eq) were added sequentially. After stirring at 0° C. for 45 min, the mixture was warmed to reflux and was stirred overnight. The reaction was then treated with sodium triacetoxyborohydride (339 mg, 1.6 mmol) at room temperature. The reaction mixture was stirred for 5 h, and then the reaction mixture was quenched with water (10 mL). The layers were filtered, and the pH was adjusted to 9 using saturated NaHCO3. The layers were then separated, and the aqueous layer was re-extracted with CH2Cl2 (2×), dried over sodium sulfate, filtered and concentrated in vacuo. The oily crude residue was converted to HCl salt using HCl/diethyl ether to provide the title compound as a beige solid (81 mg; 38%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36-1.42 (m, 1 H) 1.51-1.59 (t, 1H) 1.91-2.20 (m, 4H) 2.22-2.34 (m, 1H) 2.62 (d, 3H) 2.74 (d, 3H) 4.03-4.13 (m, 1H) 7.15 (d, 1 H) 7.37-7.46 (m, 2 H) 12.07-12.28 (bs, 1 H). 13C NMR (100 MHz, CHLOROFORM-d) d ppm 12.10 (s, 1 C) 25.73 (s, 1 C) 26.34 (s, 1 C) 31.69 (s, 1 C) 32.70 (s, 1 C) 43.47 (s, 1 C) 44.49 (s, 1 C) 74.93 (s, 1 C) 127.47 (s, 1 C) 130.12 (s, 1 C) 131.31 (s, 1 C) 131.47 (s, 1C) 133.44 (s, 1 C) 142.35 (s, 1 C). MS (M+1) 270.1, HPLC Purity 99% (AUC).

Workup

  1. temperaturethe mixture was warmed
  2. temperatureto reflux
  3. stirringwas stirred overnight
  4. stirringThe reaction mixture was stirred for 5 h
  5. customthe reaction mixture was quenched with water (10 mL)
  6. filtrationThe layers were filtered
  7. customThe layers were then separated
  8. extractionthe aqueous layer was re-extracted with CH2Cl2 (2×)
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-90010fae891743dca02a50559b0f64df
Source dataset
uspto-grants-2012_03
Patent number
US08138377B2

Reaction notes

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