4-Fluoro-3-nitrobenzoic acid → HCID 86714406, compound

HRID 1750192Notes

Reaction equation

HRID 1750192 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.Cl.[C:34]([O:38][C:39](=[O:46])[C@H:40]([CH2:42][CH:43]([CH3:45])[CH3:44])[NH2:41])([CH3:37])([CH3:36])[CH3:35]>CN(C=O)C.C(Cl)CCl>[C:34]([O:38][C:39](=[O:46])[C@@H:40]([NH:41][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=1)[CH2:42][CH:43]([CH3:44])[CH3:45])([CH3:36])([CH3:35])[CH3:37]

Participants

7

Reactant 4

HCID 679874-Fluoro-3-nitrobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine2×HCID 12451443tert-butyl (2S)-2-amino-4-methylpentanoate hydrochloride

Product 1

HCID 86714406HCID 86714406, compoundYield 100%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 9.26 g of 4-fluoro-3-nitro-benzoic acid in 100 ml of dry DMF 7.43 g of HOBT, 10.54 g of EDC and 8.9 ml of DIPEA were added at 0° C. After 30 min 12.31 g of L-leucin-tert.-butylester-hydrochloride and 8.9 ml of DIPEA were added and the reaction was stirred at it for 4 h. The reaction was then concentrated to about a fifth of its volume and poured into water. It was then extracted with ethyl acetate three times. The combined organic phases were washed with saturated aqueous sodium carbonate solution and brine, dried over magnesium sulphate and concentrated to yield 17.65 g (100%) of (S)-2-(4-Fluoro-3-nitro-benzoylamino)-4-methyl-pentanoic acid tert-butyl ester as a brown oil, which was used without further purification in the subsequent step.

Workup

  1. concentrationThe reaction was then concentrated to about a fifth of its volume
  2. additionpoured into water
  3. extractionIt was then extracted with ethyl acetate three times
  4. washThe combined organic phases were washed with saturated aqueous sodium carbonate solution and brine
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5a516e1bcd984c9ca3a66ea79a66fe2a
Source dataset
uspto-grants-2015_10
Patent number
US09156796B2

Reaction notes

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