2-Chloro-4-nitrobenzoic acid → HCID 13586207, compound

HRID 2051567Notes

Reaction equation

HRID 2051567 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.Cl.[CH2:15]([O:17][C:18](=[O:28])[C@H:19]([CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])[NH2:20])[CH3:16].ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.CO>[N+:11]([C:9]1[CH:8]=[CH:7][C:3]([C:4]([NH:20][C@H:19]([C:18]([O:17][CH2:15][CH3:16])=[O:28])[CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[O:6])=[C:2]([Cl:1])[CH:10]=1)([O-:13])=[O:12]

Participants

8

Reactant 5

HCID 74482-Chloro-4-nitrobenzoic acidHCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 757711-Hydroxybenzotriazole

Product 1

HCID 13586207HCID 13586207, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 2-chloro-4-nitrobenzoic acid (10.0 g, 49.6 mmoles), (L)-glutamate diethyl ester hydrochloride (11.9 g, 49.6 mmoles), and 1-hydroxybenzotriazole (6.7 g, 49.6 mmoles) in dry dimethylformamide (2150 mL) was stirred under nitrogen while triethylamine (5.02 g, 6.92 mL, 49.6 mmoles) was added dropwise during 1 minute. After 15 minutes, 1,3-dicyclohexylcarbodiimide (11.3 g, 54.6 mmoles) was added in portions during 1 minute. The reaction mixture was filtered after 18 hours and the solids were rinsed with dichloromethane (2×50 mL). The filtrate was spin evaporated (high vacuum) to an amber residue that was dissolved in dichloromethane (300 mL). The organic phase was washed successively with saturated bicarbonate, 5% citric acid, and brine solution (1×300 mL each). The organic phase was then dried (MgSO4), filtered, and poured onto a silica gel column (500 g, pre-wet with dichloromethane). The column was rinsed with dichloromethane (500 mL), followed by gradient elution of the product with 10% and 15% added ethyl acetate (8×250 mL fractions each). Like fractions were combined by spin evaporation and dried to give a white solid; yield, 9.8 g (51%); mp 95°-96° C.; 1H-NMR (DMSO-d6) δ 1.17 and 1.21 (2t overlapped, 6H), 1.8-2.2 (m, 2H), 2.46 (t obscured by DMSO, 2H), 4.0-4.2 (2 q overlapped, 4H), 4.46 (m, 1H), 7.68 (d, Jo =8 Hz, 1H), 8.25 (dxd, Jo =8 Hz, Jm =2 Hz, 1H), 8.34 (d, Jm 2 Hz, 1H), 9.14 (d, 1H); uv (MeOH) 260 nm max (9930), 236 min (6180), 205 max (25600); mass spec (CI) m/e 387 (100%), 341 (40), 184 (21).

Workup

  1. additionwas added dropwise during 1 minute
  2. filtrationThe reaction mixture was filtered after 18 hours
  3. washthe solids were rinsed with dichloromethane (2×50 mL)
  4. customevaporated (high vacuum) to an amber residue that
  5. dissolutionwas dissolved in dichloromethane (300 mL)
  6. washThe organic phase was washed successively with saturated bicarbonate, 5% citric acid, and brine solution (1×300 mL each)
  7. dry with materialThe organic phase was then dried (MgSO4)
  8. filtrationfiltered
  9. additionpoured onto a silica gel column (500 g, pre-wet with dichloromethane)
  10. washThe column was rinsed with dichloromethane (500 mL)
  11. washfollowed by gradient elution of the product with 10% and 15%
  12. additionadded ethyl acetate (8×250 mL fractions each)
  13. customLike fractions were combined by spin evaporation
  14. customdried
  15. customto give a white solid
  16. customyield

Sources & evidence

ORD record
ord-da71c9d959f244058a2e4b74084cfbea
Source dataset
uspto-grants-1991_05
Patent number
US05019577

Reaction notes

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