3-Hydroxy-2,2-dimethylpropionic acid → HCID 86692262, compound

HRID 1469785Notes

Reaction equation

HRID 1469785 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:15])=[C:5]([C:11]([Cl:14])=[CH:12][CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7].[OH:16][CH2:17][C:18]([CH3:23])([CH3:22])[C:19](O)=[O:20].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[Cl:14][C:11]1[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([F:15])[C:3]([CH2:2][NH:1][C:17](=[O:16])[C:18]([CH3:23])([CH3:22])[CH2:19][OH:20])=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 785483-Hydroxy-2,2-dimethylpropionic acidHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 58483233Ethyl 3-(aminomethyl)-6-chloro-2-fluorobenzoate

Product 1

HCID 86692262HCID 86692262, compoundYield 61.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ethyl 3-(aminomethyl)-6-chloro-2-fluorobenzoate (Intermediate-2, step-1, 800 mg, 3.45 mmol) and 3-hydroxy-2,2-dimethylpropanoic acid (591 mg, 5.00 mmol) in DMF (5 mL) were added (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (2.29 g, 5.18 mmol) and DIPEA (1.29 g, 10.0 mmol). Then reaction mixture was stirred at rt for 12 h and it was diluted with EtOAc, washed with H2O and brine. The organic layer was separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 700 mg of the title product. 1H NMR (400 MHz, DMSO d6): δ 8.09-8.06 (t, J=8.0 Hz, 1H), 7.45-7.38 (m, 2H), 4.91-4.88 (t, J=5.2 Hz, 1H), 4.42-4.37 (q, J=8.0 Hz, 2H), 4.29-4.28 (d, J=5.6 Hz, 2H), 3.48 (m, 2H), 1.33-1.29 (t, J=8.0 Hz, 3H), 1.05 (s, 6H).

Workup

  1. customThen reaction mixture
  2. washwashed with H2O and brine
  3. customThe organic layer was separated
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-2e199219227b4aa9b768a8ea39838352
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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