Hydrochloric Acid → HCID 22969540, compound

HRID 1278891Notes

Reaction equation

HRID 1278891 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:27])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C@@H:23]([OH:26])[CH2:24][OH:25])[CH:16]=1.C(N(CC)CC)C.[C:35](Cl)(Cl)=[O:36].Cl>C1COCC1.C(OCC)(=O)C.O>[NH2:1][C:2]1[N:6]([C:7]2[CH:8]=[CH:9][C:10]([F:13])=[CH:11][CH:12]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:27])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C@@H:23]2[CH2:24][O:25][C:35](=[O:36])[O:26]2)[CH:16]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6371PhosgeneHCID 8471TriethylamineHCID 5327067HCID 5327067, compound

Product 1

HCID 22969540HCID 22969540, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-5 °C

Procedure

To a suspension of 15.0 g (40.4 mmol) of 5-amino-1-(4-fluorophenyl)-4-[3-{2(S),3-dihydroxypropoxy}benzoyl]pyrazole in 150 ml THF was added 17 ml (168 mmol) of triethylamine. The mixture was cooled to −5° C. and 18 ml of phosgene (20% in toluene) was added over a 30 minute period keeping the reaction temperature below 0° C. Once addition was complete, the reaction was stirred for an additional hour at 0° C. Then, 20 ml of distilled water was added along with 5% HCl until the pH of the solution was 5 to 6. After 30 minutes, ethyl acetate was added and the organic layer was separated, washed with brine, and dried over MgSO4. Filtration and concentration in vacuo gave a yellow oil which was purified by flash column chromatography using 1:1-1:2 hexanes/ethyl acetate as eluent. The desired carbonate precipitated upon concentrating the column fractions to give 7.38 g of desired product.

Workup

  1. customthe reaction temperature below 0° C
  2. additionOnce addition
  3. customthe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationFiltration and concentration in vacuo
  7. customgave a yellow oil which
  8. customwas purified by flash column chromatography
  9. customThe desired carbonate precipitated
  10. concentrationupon concentrating the column fractions

Sources & evidence

ORD record
ord-c5037efb5b264ce6ba85407fff32cd77
Source dataset
uspto-grants-2002_09
Patent number
US06444696B1

Reaction notes

Loading…