Acetic Anhydride → tert-Butyl 4-(3-acetamido-4-(acetamidomethyl)phenyl)piperazine-1-carboxylate

HRID 1406617Notes

Reaction equation

HRID 1406617 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:5][C:4]=1[N+:22]([O-])=O)#[N:2].[C:25](OC(=O)C)(=[O:27])[CH3:26].C1C[O:35][CH2:34][CH2:33]1>[Ni]>[C:25]([NH:22][C:4]1[CH:5]=[C:6]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[CH:7]=[CH:8][C:3]=1[CH2:1][NH:2][C:34](=[O:35])[CH3:33])(=[O:27])[CH3:26]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8028TetrahydrofuranHCID 51354044Tert-butyl 4-(4-cyano-3-nitrophenyl)piperazine-1-carboxylate

Product 1

HCID 131732195tert-Butyl 4-(3-acetamido-4-(acetamidomethyl)phenyl)piperazine-1-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Procedure

To a solution of compound 18 (2.0 g, 6 mmol) in THF (30 mL) was added acetic anhydride (4.5 mL, 48 mmol), followed by the addition of Ra—Ni (˜0.4 g), and the mixture was subjected to hydrogenation in a Parr apparatus at 60 psi for 12 h. After filtering over the pad of celite, the solution was concentrated to get a brown oil material, which was resolved over silica column eluting with EtOAc:hexanes (4:6) and then changing to (6:4) to get 1.75 g (75%) of 19 as an off-white gum. IR (KBr) νmax. cm−1: 3311, 3160 (NH), 3062 (Ar—H), 1691 (C═O), 1611, 1512, 1412 (C═C). 1H NMR (500 MHz, CDCl3)=1.39 (s, 9H, (CH3)3C); 1.98 (s, 3H, CH3); 2.21 (s, 3H, CH3); 3.03 (m, 4H, 2CH2); 3.53 (m, 4H, 2CH2); 4.29 (d, 2H, J=6.7 Hz, CH2); 6.73 (d, 1H, J=2.4 Hz, H-2); 6.84 (dd, 1H, J=8.8, J=2.4 Hz, H-6); 7.85 (d, 1H, J=8.8 Hz, H-5); 9.48 (s, 1H, NH); 13C NMR (125.7 MHz, CDCl3) δ=22.96 (CH3), 24.06 (CH3), 28.37 (CH3)3C), 40.87 (CH2), 43.50 (CH2), 49.73 (CH2), 79.95 (CH3)3C), 117.14 (C-2), 118.65 (C-4), 124.56 (C-6), 129.59 (C-3), 129.94 (C-5), 147.95 (C-1), 154.67 (C═O), 169.41 (C═O), 171.29 (C═O). Calculated (%) for C20H30N4O4 (390.23); C, 61.52; H, 7.74; N, 14.35. found (%); C, 61.43; H, 7.82; N, 14.26.

Workup

  1. filtrationAfter filtering over the pad of celite
  2. concentrationthe solution was concentrated
  3. customto get a brown oil material, which
  4. washeluting with EtOAc:hexanes (4:6)

Sources & evidence

ORD record
ord-37093c8a932d44739794b70d42266bb3
Source dataset
uspto-grants-2014_12
Patent number
US08916704B1

Reaction notes

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