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

HRID 2424628Notes

Reaction equation

HRID 2424628 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

D5 (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 triacetoxyborohydride (781 mg, 3.7 mmol) were stirred together in 1,2-DCE (15 mL) for 17 h. Saturated aqueous NaHCO3 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. The crude product was purified by chromatography. Elution with 0-100% EtOAc/petroleum ether yielded the title compound as a colourless oil (573 mg). δH (CDCl3, 400 MHz) 7.28 (2H, m), 7.15 (2H, m), 4.17 (1H, br.s), 3.76 (1H, d), 3.36 (2H, s), 3.00 (1H, m), 2.70 (1H, d), 2.56 (1H, d), 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. customThe crude product was purified by chromatography
  6. washElution with 0-100% EtOAc/petroleum ether

Sources & evidence

ORD record
ord-4a7c9ec4326f4ef68c964de3085993e2
Source dataset
uspto-grants-2011_06
Patent number
US07964597B2

Reaction notes

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