Triethylamine → HCID 67278263, compound

HRID 1694402Notes

Reaction equation

HRID 1694402 reaction equation
[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([Cl:12])[CH:3]=1.[CH2:13]([N:15](CC)[CH2:16][CH3:17])[CH3:14].N1CCCC1.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC>CCOC(C)=O>[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([N:15]2[CH2:16][CH2:17][CH2:14][CH2:13]2)=[O:8])=[C:4]([Cl:12])[CH:3]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 31268PyrrolidineHCID 111923Propylphosphonic anhydrideHCID 27362254-Bromo-2-chloro-5-fluorobenzoic acid

Product 1

HCID 67278263HCID 67278263, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a stirring solution of 4-bromo-2-chloro-5-fluorobenzoic acid (50 g, 0.25 mol) in 200 mL of EtOAc at 0° C. (ice/water bath) was added triethyl amine (237 mL, 0.50 mol), pyrrolidine (41.2 mL, 0.5 mol), followed by 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide (CAS # 68957-94-8) (237 mL, 0.37 mol, 50 wt %, EtOAc). After 1 hr, the reaction was quenched with a saturated solution of NaHCO3, and extracted with EtOAc, and CH2Cl2. The combined organic layers were dried over MgSO4, filtered and concentrated. Purification of this material was accomplished by flash column chromatography using a Biotage™ 75L column, eluting with a gradient of 2%-50% EtOAc/hexanes. The product containing fractions were collected and concentrated to give the title compound (52 g, 68% yield) as a white solid: Rf=0.23 (40% EtOAc/hexanes): LRMS m/z Calcd for C11H10BrClFNO, 306.6, found, 306, 308, 310 (M+1) APCI; 1H NMR (300 MHz, CDCl3): δ 7.53 (d, J=6.2 Hz, 1H), 7.02 (d J=7.9 Hz, 1H), 3.54 (apt t, J=6.6 Hz, 2H), 3.13 (apt t, J=6.6 Hz, 2H), 1.92-1.83 (m, 4H); 100 MHz 13C NMR (CDCl3) δ 164.5, 158.1 (d, JC-F=249.5 Hz), 138.2, 134.3, 126.0, 115.5 (d, JC-F=25.5 Hz), 110.3 (d, JC-F=22.5 Hz), 47.0, 45.8, 26.0, 24.6.

Workup

  1. customthe reaction was quenched with a saturated solution of NaHCO3
  2. extractionextracted with EtOAc, and CH2Cl2
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of this material
  7. washeluting with a gradient of 2%-50% EtOAc/hexanes
  8. additionThe product containing fractions
  9. customwere collected
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-0c47d12b129941b4b4a9e45d92196bc5
Source dataset
uspto-grants-2012_04
Patent number
US08158673B2

Reaction notes

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