Triphenylphosphine → HCID 86714622, compound

HRID 1409302Notes

Reaction equation

HRID 1409302 reaction equation
[Cl:1][C:2]1[C:9]([F:10])=[C:8]([C:11]2[NH:15][N:14]=[CH:13][CH:12]=2)[CH:7]=[C:6]([F:16])[C:3]=1[C:4]#[N:5].O[CH2:18][C@@H:19]([NH:21]C(=O)OC(C)(C)C)[CH3:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>C1COCC1>[NH2:21][C@@H:19]([CH3:20])[CH2:18][N:14]1[CH:13]=[CH:12][C:11]([C:8]2[CH:7]=[C:6]([F:16])[C:3]([C:4]#[N:5])=[C:2]([Cl:1])[C:9]=2[F:10])=[N:15]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 70231031,1-Dimethylethyl N-((1S)-2-hydroxy-1-methylethyl)carbamateHCID 86714621HCID 86714621, compound

Product 1

HCID 86714622HCID 86714622, compoundYield 67.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

2-Chloro-3,6-difluoro-4-(1H-pyrazol-5-yl)benzonitrile (0.835 mmol, 0.2 g) was dissolved in THF under nitrogen atmosphere. (S)-tert-butyl (1-hydroxypropan-2-yl)carbamate (0.835 mmol, 0.146 g) and triphenylphosphine (1.252 mmol, 0.328 g) were dissolved in THF and added to the previous mixture. The resulting mixture was cooled to 0° C. Di-tert-butyl azodicarboxylate (1.252 mmol, 0.288 g) was added in small portions and stirred under cold conditions for 10 min. The flask was warmed to RT and stirred overnight. The solvent was evaporated. The residue was dissolved in ethanol and 10% HCl(g)/EtOH solution (15 ml) was slowly added. The resulting mixture was stirred overnight. The mixture was diluted with water and extracted twice with DCM. The combined organics were washed with water. The aqueous phases were combined and the pH was adjusted to 12 with 2 M NaOH. The aqueous phase was extracted three times with DCM. The combined organics were dried, filtered and evaporated. 0.167 g of the title compound was obtained. 1H-NMR (400 MHz, CDCl3): δ 1.17 (d, 3H), 1.31 (bs, 2H), 3.53 (bs, 1H), 3.88-4.04 (m, 1H), 4.09-4.26 (m, 1H), 6.82 (dd, 1H), 7.55 (d, 1H), 7.88 (dd, 1H).

Workup

  1. additionadded to the previous mixture
  2. temperatureThe flask was warmed to RT
  3. stirringstirred overnight
  4. customThe solvent was evaporated
  5. dissolutionThe residue was dissolved in ethanol
  6. addition10% HCl(g)/EtOH solution (15 ml) was slowly added
  7. stirringThe resulting mixture was stirred overnight
  8. additionThe mixture was diluted with water
  9. extractionextracted twice with DCM
  10. washThe combined organics were washed with water
  11. extractionThe aqueous phase was extracted three times with DCM
  12. customThe combined organics were dried
  13. filtrationfiltered
  14. customevaporated

Sources & evidence

ORD record
ord-27e989305f5a44e4b5e29e339d2ce196
Source dataset
uspto-grants-2014_12
Patent number
US08921378B2

Reaction notes

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