5-Chloro-2-nitrobenzoic acid → HCID 57725370, compound

HRID 1091433Notes

Reaction equation

HRID 1091433 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N+:11]([O-:13])=[O:12])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.Cl.[C:15]([O:19][C:20](=[O:25])[C@@H:21]([NH2:24])[CH2:22][CH3:23])([CH3:18])([CH3:17])[CH3:16].C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>O1CCCC1.CN(C1C=CN=CC=1)C.C(Cl)CCl>[C:15]([O:19][C:20](=[O:25])[C@@H:21]([NH:24][C:7](=[O:9])[C:6]1[CH:10]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=1[N+:11]([O-:13])=[O:12])[CH2:22][CH3:23])([CH3:17])([CH3:16])[CH3:18]

Participants

8

Reactant 4

HCID 172865-Chloro-2-nitrobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 53628861tert-Butyl (2S)-2-aminobutanoate--hydrogen chloride (1/1)

Product 1

HCID 57725370HCID 57725370, compoundYield 85.7%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-chloro-2-nitro-benzoic acid (4.68 g) in anhydrous tetrahydrofuran (100 ml) at 0° C., was added (S)-2-amino-butyric acid-tert-butyl ester hydrochloric acid salt (5 g), HOBt (3.45 g), DMAP (2.98 g), followed by EDC (4.88 g) and diisopropylethylamine (3.30 g). The reaction mixture was stirred for 10 minutes then warmed to room temperature and stirred for 16 hours before concentration at reduced pressure. The resulting residue was partitioned between EtOAc (100 ml) and saturated sodium bicarbonate solution (100 ml), the organic layer separated and further washed with 1M hydrochloric acid and saturated brine solution, dried (MgSO4), filtered and concentrated to give the sub-title compound as a pale yellow oil (6.82 g, 68% yield). 1H NMR (400 MHz, CDCl3) δ 8.05 (1H, d), 7.55 (2H, m), 6.4 (1H, m) 4.7 (1H, m), 2.1 (1H, m), 1.95 (1H, m), 1.5 (9H, s), 1.0 (3H, t) ppm.

Workup

  1. stirringstirred for 16 hours before concentration at reduced pressure
  2. customThe resulting residue was partitioned between EtOAc (100 ml) and saturated sodium bicarbonate solution (100 ml)
  3. customthe organic layer separated
  4. washfurther washed with 1M hydrochloric acid and saturated brine solution
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e9c92621a5524a60a88a69962a498714
Source dataset
uspto-grants-2012_03
Patent number
US08129381B2

Reaction notes

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