p-(Trifluoromethoxy)benzaldehyde → HCID 57565304, compound

HRID 1172199Notes

Reaction equation

HRID 1172199 reaction equation
[F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1.[CH3:14][C@H:15]1[CH2:20][NH:19][CH2:18][C@@H:17]([CH3:21])[NH:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:14][C@H:15]1[NH:16][C@@H:17]([CH3:21])[CH2:18][N:19]([CH2:8][C:7]2[CH:10]=[CH:11][C:4]([O:3][C:2]([F:13])([F:12])[F:1])=[CH:5][CH:6]=2)[CH2:20]1

Participants

5

Reactant 3

HCID 69573p-(Trifluoromethoxy)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 6950261rel-(2R,6S)-2,6-dimethylpiperazine

Product 1

HCID 57565304HCID 57565304, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(trifluoromethoxy)-benzaldehyde (776 uL, 4.38 mmol) in methylene chloride (30 mL) was added cis-2,6-dimethyl piperazine (1.0 g, 8.77 mmol). After 1 hour sodium triacetoxy borohydride (2.45 g, 8.77 mmol) was added to the mixture. The solution was stirred at room temperature for an additional 4 hours. The reaction was concentrated in vacuo, diluted with ethyl acetate and extracted with 1N HCl (2×50 mL). The aqueous layer was then neutralized with NaOH and extracted with ethyl acetate (3×50 mL). The organic layer was dried (Na2SO4) and concentrated to provide cis-3,5-dimethyl-1-(4-trifluoromethoxy-benzyl)-piperazine (1.01 g, 80%). 1H NMR (400 MHz, CD3OD) δ 7.42 (d, 2H), 7.23 (d, 2H), 3.54 (s, 2H), 2.98-2.88 (m, 2H), 2.82-2.74 (m, 2H), 1.69 (t, 2H), 1.05 (d, 6H); LCMS 289.5 (M+1)+.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. additiondiluted with ethyl acetate
  3. extractionextracted with 1N HCl (2×50 mL)
  4. extractionextracted with ethyl acetate (3×50 mL)
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f67b9321896042188beed564c6e17236
Source dataset
uspto-grants-2010_11
Patent number
US07834004B2

Reaction notes

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