Ethylamine hydrochloride → 4-Chloro-N-ethyl-3',5'-difluoro-6-(1-hydroxyethyl)-3-methylbiphenyl-2-carboxamide

HRID 1499725Notes

Reaction equation

HRID 1499725 reaction equation
[Cl:1][C:2]1[C:3]([CH3:22])=[C:4]([C:19](O)=[O:20])[C:5]([C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=2)=[C:6]([CH:8]([OH:10])[CH3:9])[CH:7]=1.Cl.[CH2:24]([NH2:26])[CH3:25].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C=O>[Cl:1][C:2]1[C:3]([CH3:22])=[C:4]([C:19]([NH:26][CH2:24][CH3:25])=[O:20])[C:5]([C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=2)=[C:6]([CH:8]([OH:10])[CH3:9])[CH:7]=1

Participants

6

Reactant 4

HCID 11198Ethylamine hydrochlorideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 866776604-Chloro-3',5'-difluoro-6-(1-hydroxyethyl)-3-methylbiphenyl-2-carboxylic acid

Product 1

HCID 866776614-Chloro-N-ethyl-3',5'-difluoro-6-(1-hydroxyethyl)-3-methylbiphenyl-2-carboxamideYield 68.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-chloro-3′,5′-difluoro-6-(1-hydroxyethyl)-3-methylbiphenyl-2-carboxylic acid (250 mg, 0.76 mmol), ethylamine hydrochloride (94 mg, 1.1 mmol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.51 g, 1.1 mmol) in N,N-dimethylformamide (4 mL) was stirred at rt for 10 min. To the resulting mixture was added N,N-diisopropylethylamine (0.40 mL, 2.3 mmol). After stirred at rt overnight, the reaction was quenched with water, extracted with EtOAc. The combined organic layers were washed with water, brine, dried over magnesium sulfate, and then concentrated to dry. The residue was purified on silica gel, eluting with 0 to 80% EtOAc in hexanes, to give the desired product (185 mg, 68%). LCMS calculated for C18H19ClF2NO2 (M+H)+: m/z=354.1; Found: 354.0.

Workup

  1. stirringAfter stirred at rt overnight
  2. customthe reaction was quenched with water
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customto dry
  8. customThe residue was purified on silica gel
  9. washeluting with 0 to 80% EtOAc in hexanes

Sources & evidence

ORD record
ord-f59401c88f384902b1561d8c7253d209
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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