Formic Acid → N,N-Diethylbenzamide

HRID 1460099Notes

Reaction equation

HRID 1460099 reaction equation
[Si](OC1C=C(C=CC=1)C([C:21]1[CH:33]=[CH:32][C:24]([C:25]([N:27]([CH2:30][CH3:31])[CH2:28][CH3:29])=[O:26])=[CH:23][CH:22]=1)N1C[C@H](C)N[C@H](C)C1)(C(C)(C)C)(C)C.C(O)=O.C=O>Cl>[CH2:30]([N:27]([CH2:28][CH3:29])[C:25](=[O:26])[C:24]1[CH:32]=[CH:33][CH:21]=[CH:22][CH:23]=1)[CH3:31]

Participants

5

Reactant 3

HCID 284Formic AcidHCID 712FormaldehydeHCID 22875660HCID 22875660, compound

Product 1

HCID 15542N,N-Diethylbenzamide

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (±)-4-(3-((tert-butyldimethylsilyl)oxy)-α-(cis-3,5-dimethyl-1-piperazinyl)benzyl)-N,N-diethylbenzamide (18.5 g, 36.5 mmol) (from Example 11), 88% formic acid (5.1 g, 110 mmol) and 37.6% formaldehyde (2.8 g, 95 mmol) was heated at 80° C. overnight. The reaction mixture was cooled to room temperature and 20 mL of 7.2M hydrochloric acid was added slowly. The mixture was washed three times with 40 mL of dichloromethane. The pH of the aqueous layer was adjusted to 8 with a saturated solution of sodium bicarbonate and then extracted with 3×40 mL of dichloromethane. The organic extracts were dried over magnesium sulfate and evaporated to dryness to give 12.6 g (84%) of (±)-4-(3-hydroxy)-α-(cis 3,4,5-trimethyl-1-piperazinyl)benzyl)-N,N-diethylbenzamide as a tan foam. NMR (300 MHz, CDCl3): δ 1.0-1.3 (br m, 2d, J=6 Hz and J=6 Hz, 12H); 2.3 (br dd, 2H), 2.6 (s, 3H); 2.7-3.0 (br m, 4H); 3.2-3.6 (br m, 4H); 4.2 (s, 1H), 6.7 (d, J=7 Hz, 1H); 6.8 (d, J=8 Hz, 1H); 6.9 (s, 1H); 7.1 (t, J=8 Hz, 1H); 7.25 and 7.40 (AB q, J=8 Hz, 4H). A portion of the product was dissolved in dichloromethane:ethanol and converted to the dihydrochloride salt with an excess of ethereal hydrogen chloride. The solvent was removed and the residue was redissolved in a minimum amount of dichloromethane. Diethyl ether was added to give an oily precipitate which solidified with stirring. Filtration gave the hydrated dihydrochloride salt. Calc. for C25H35N3O2 2 HCl 1.5 H2O: C, 58.93; H, 7.91; N, 8.25; Cl, 13.92. Found: C, 58.84; H, 7.89; N, 8.09; Cl, 13.69.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe mixture was washed three times with 40 mL of dichloromethane
  3. extractionextracted with 3×40 mL of dichloromethane
  4. dry with materialThe organic extracts were dried over magnesium sulfate
  5. customevaporated to dryness

Sources & evidence

ORD record
ord-d6cf5cd6346c4c21a46ebb6c423f251a
Source dataset
uspto-grants-1998_12
Patent number
US05854249

Reaction notes

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