Sodium hydride → HCID 71477845, compound

HRID 707785Notes

Reaction equation

HRID 707785 reaction equation
[Br:1][C:2]1[C:10]2[N:9]=[CH:8][NH:7][C:6]=2[C:5]([Br:11])=[C:4]([Br:12])[C:3]=1[Br:13].[H-].[Na+].C[O:17][C:18](=[O:27])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]Br>CN(C=O)C>[Br:11][C:5]1[C:6]2[N:7]=[CH:8][N:9]([CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][C:18]([OH:27])=[O:17])[C:10]=2[C:2]([Br:1])=[C:3]([Br:13])[C:4]=1[Br:12]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 51497394,5,6,7-tetrabromobenzimidazoleHCID 11107373Methyl 8-bromooctanoate

Product 1

HCID 71477845HCID 71477845, compoundYield 63.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4,5,6,7-tetrabromo-1H-benzimidazole (115 mg, 0.26 mmol) and NaH suspension (12 mg, ˜0.28 mmol) were stirred in DMF for 30 min and then 8-bromooctanoic acid methyl ester (182 mg, 0.77 mmol) was added. The solution was stirred for 2 days and then evaporated to dryness. The residue was purified by flash chromatography (CHCl3: methanol; 20:1 by volume). The methyl ester was hydrolyzed in the mixture of methanol and aqueous KOH for 1 hour and the solvents were removed in vacuum. The obtained residue was partitioned between ethyl acetate and KHSO4, the organic layer was dried and evaporated to yield 8-(4,5,6,7-tetrabromo-1H-benzimidazole-1-yl)octanoic acid (95 mg, 62% over two steps). 1H NMR (200 MHz; DMSO6d; Me4Si) 1.28 (m, 6H), 1.48 (m, 2H), 1.76 (m, 2H), 2.19 (t, J=7.3 Hz, 2H), 4.48 (t, J=7.6 Hz, 2H), 8.51 (s, 1H), 11.91 (br, 1H). 13C NMR (50 MHz; DMSO6d; Me4Si) 24.3, 25.5, 28.1, 28.3, 31.5, 33.6, 46.4, 106.5, 116.6, 120.4, 122.3, 131.3, 143.7, 148.9, 174.4. B. Synthesis of TBBI-OcA-(D-Asp)-(L-Asp)5-(L-Lys)-OH

Workup

  1. customevaporated to dryness
  2. customThe residue was purified by flash chromatography (CHCl3: methanol; 20:1 by volume)
  3. additionThe methyl ester was hydrolyzed in the mixture of methanol and aqueous KOH for 1 hour
  4. customthe solvents were removed in vacuum
  5. customThe obtained residue was partitioned between ethyl acetate and KHSO4
  6. customthe organic layer was dried
  7. customevaporated

Sources & evidence

ORD record
ord-40651a3e1a18491aa2aa36b14c897353
Source dataset
uspto-grants-2015_11
Patent number
US09176064B2

Reaction notes

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