Triethylamine → 1,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylate

HRID 534761Notes

Reaction equation

HRID 534761 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[CH:5][C:4]=1[CH3:13])=O.Cl.[CH3:15][C@H:16]1[CH2:21][NH:20][CH2:19][CH2:18][N:17]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[C:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:1][N:20]2[CH2:19][CH2:18][N:17]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C@@H:16]([CH3:15])[CH2:21]2)=[C:4]([CH3:13])[CH:5]=1)(=[O:12])[CH3:11]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 12931765N-(4-Formyl-3-methylphenyl)acetamideHCID 45072182(S)-tert-butyl 2-methylpiperazine-1-carboxylate hydrochloride

Product 1

HCID 592621441,1-Dimethylethyl (2S)-4-{[4-(acetylamino)-2-methylphenyl]methyl}-2-methyl-1-piperazinecarboxylateYield 88.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

N-(4-Formyl-3-methylphenyl)acetamide (D78) (326 mg, 1.8 mmol), 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate hydrochloride (436 mg, 1.8 mmol), triethylamine (0.282 mL, 2 mmol) and sodium tri(acetoxy)borohydride (781 mg, 3.7 mmol) were stirred together in DCE (15 mL) for 17 h. Saturated aqueous NaHCO3 (15 mL) was added and the reaction mixture stirred for 1 h. The organic layer was separated and washed with water and brine, then dried and concentrated to give the crude product which was purified by chromatography. Elution with 0-100% ethyl acetate/petroleum ether yielded the title compound as a colourless oil (573 mg). δH (CDCl3, 400 MHz) 7.27 (2H, m), 7.16 (1H, d), 7.11 (1H, br.s), 4.17 (1H, m), 3.78 (1H, m), 3.36 (2H, s), 3.02 (1H, m), 2.70 (1H, m), 2.56 (1H, m), 2.36 (3H, s), 2.17 (4H, m), 1.95 (1H, m), 1.45 (9H, s), 1.18 (3H, d). MS (ES): MH+ 362.3.

Workup

  1. customThe organic layer was separated
  2. washwashed with water and brine
  3. customdried
  4. concentrationconcentrated
  5. customto give the crude product which
  6. customwas purified by chromatography
  7. washElution with 0-100% ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-d2536c0b5b9e4c6c880d90165a0b620f
Source dataset
uspto-grants-2014_10
Patent number
US08853218B2

Reaction notes

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