tert-butyl N-(4-aminobutyl)carbamate → HCID 58997198, compound

HRID 250933Notes

Reaction equation

HRID 250933 reaction equation
Cl[CH2:2][C:3]1[NH:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1.[C:12]([O:16][C:17](=[O:24])[NH:18][CH2:19][CH2:20][CH2:21][CH2:22][NH2:23])([CH3:15])([CH3:14])[CH3:13].CCN(C(C)C)C(C)C>CC#N>[C:12]([O:16][C:17](=[O:24])[NH:18][CH2:19][CH2:20][CH2:21][CH2:22][NH:23][CH2:2][C:3]1[NH:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1)([CH3:15])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 4351tert-butyl N-(4-aminobutyl)carbamateHCID 785712-ChloromethylbenzimidazoleHCID 81531Diisopropylethylamine

Product 1

HCID 58997198HCID 58997198, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-Chloromethylbenzimidazole (19.81 g, 118.9 mmol) was added as a solid to a mechanically stirred and cooled (1.2° C. internal temperature) solution of (4-amino-butyl)-carbamic acid tert-butyl ester (56.0 g, 297.3 mmol) and DIPEA (51.8 mL, 297.3 mmol) in CH3CN (3 L) under N2. After 4.5 h at low temperature the cooling bath was removed and the mixture was concentrated in vacuo. The residue was taken up in CH2Cl2 (1.5 L) and washed with brine (1 L). The aqueous layer was extracted with CH2Cl2 (2×500 mL) and the combined organic layers were dried over MgSO4 and concentrated in vacuo to afford a yellow foamy solid. Purification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH (98:1:1) to CH2Cl2/MeOH/NH4OH (80:10:10)) afforded product containing mixed fractions. Repurification of these fractions by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH (98:3:3)) afforded the title compound as a yellow solid (16.5 g, 44%). 1H NMR (CDCl3) δ 1.50 (s, 9H), 1.60-1.64 (m, 4H), 2.70-2.74 (m, 2H), 3.10-3.18 (m, 2H), 4.13 (s, 2H), 4.86 (s, 1H), 7.19-7.25 (m, 2H), 7.50-7.95 (m, 2H), 10.4 (bs, 1H); 13C NMR (CDCl3) δ 26.1, 27.3, 28.1, 39.7, 41.2, 47.2, 47.7, 48.3, 49.4, 78.9, 121.7, 153.9, 155.9; ES-MS m/z 319 (M+H). Anal Calcd. For C17H26N4O2.0.2(H2O): C, 63.41; H, 8.26; N, 17.40. Found: C, 63.51; H, 8.19; N, 17.33.

Workup

  1. customAfter 4.5 h at low temperature the cooling bath was removed
  2. concentrationthe mixture was concentrated in vacuo
  3. washwashed with brine (1 L)
  4. extractionThe aqueous layer was extracted with CH2Cl2 (2×500 mL)
  5. dry with materialthe combined organic layers were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto afford a yellow foamy solid
  8. customPurification by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH (98:1:1) to CH2Cl2/MeOH/NH4OH (80:10:10))
  9. customafforded product
  10. additioncontaining
  11. additionmixed fractions
  12. customRepurification of these fractions by column chromatography on silica gel (CH2Cl2/MeOH/NH4OH (98:3:3))

Sources & evidence

ORD record
ord-7badacb08bbb476281a095069919f3d9
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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