Sodium Bicarbonate → HCID 86724133, compound

HRID 1748804Notes

Reaction equation

HRID 1748804 reaction equation
C([Li])CCC.[Cl-].[CH3:7][O:8][CH2:9][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Br:29][C:30]1[CH:35]=[CH:34][C:33]([CH:36]([C:40]2[C:41]([C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][N:56]=3)=[N:42][N:43]([CH2:53][CH3:54])[C:44]=2[NH:45][C:46](=[O:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])[CH2:37][CH:38]=O)=[CH:32][CH:31]=1.C([O-])(O)=O.[Na+]>CCOC(C)=O.C1COCC1>[Br:29][C:30]1[CH:35]=[CH:34][C:33]([CH:36]([C:40]2[C:41]([C:55]3[CH:60]=[CH:59][CH:58]=[CH:57][N:56]=3)=[N:42][N:43]([CH2:53][CH3:54])[C:44]=2[NH:45][C:46](=[O:52])[O:47][C:48]([CH3:50])([CH3:51])[CH3:49])[CH2:37][CH:38]=[CH:7][O:8][CH3:9])=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 86724132HCID 86724132, compoundHCID 178418339Butyllithium

Product 1

HCID 86724133HCID 86724133, compoundYield 82.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

n-Butyllithium (1.6 M solution in hexanes, 0.980 mL, 1.57 mmol) was added dropwise over about 10 min to a slurry of (methoxymethyl)triphenylphosphonium chloride (0.550 g, 1.60 mmol) and THF (3.00 mL) under N2 at about −78° C. After about 5 min, the reaction vessel was transferred to an ice water bath. After stirring for about 10 min at about 0° C., the dark red reaction mixture was cooled to about −78° C. A solution of tert-butyl (4-(1-(4-bromophenyl)-3-oxopropyl)-1-ethyl-3-(pyridin-2-yl)-1H-pyrazol-5-yl)carbamate (0.161 g, 0.168 mmol) and THF (1.50 mL) was added over about 5 min. After about 5 min, the reaction mixture was transferred to an ice bath. After about 1 h, saturated aqueous NaHCO3 (5 mL) and EtOAc (5 mL) were added respectively. The ice bath was removed. The layers were separated and the aqueous layer was extracted with EtOAc (5 mL). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified on silica gel using a gradient of 10-50% EtOAc in heptane. The fractions containing product were combined and concentrated under reduced pressure to afford tert-butyl (4-(1-(4-bromophenyl)-4-methoxybut-3-en-1-yl)-1-ethyl-3-(pyridin-2-yl)-1H-pyrazol-5-yl)carbamate (0.0726 g, 0.138 mmol, 82%) as an ivory solid. Compound was about a 2.2:1 mixture of olefin isomers. LC-MS (Table 1, Method g) Rt=2.83 min; m/z 527 and 529 (M+H)+(Major) and Rt=2.87 min; m/z 527 and 529 (M+H)+ (Minor).

Workup

  1. customthe reaction vessel was transferred to an ice water bath
  2. customthe dark red reaction mixture
  3. temperaturewas cooled to about −78° C
  4. waitAfter about 5 min
  5. customthe reaction mixture was transferred to an ice bath
  6. waitAfter about 1 h
  7. customThe ice bath was removed
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with EtOAc (5 mL)
  10. dry with materialThe combined organics were dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was purified on silica gel using a gradient of 10-50% EtOAc in heptane
  14. additionThe fractions containing product
  15. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c3ee71322fa04e56be88b50d14724574
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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