Triphenylphosphine → HCID 67432750, compound

HRID 1040158Notes

Reaction equation

HRID 1040158 reaction equation
[N:1]([CH2:4][C:5]1[CH:6]=[C:7]([C:22]2[S:26][C:25]([C@@:27]3([OH:39])[CH2:32][CH2:31][C@H:30]([C:33]([O:35][CH3:36])=[O:34])[C:29]([CH3:38])([CH3:37])[CH2:28]3)=[N:24][CH:23]=2)[CH:8]=[C:9]([NH:11][C:12]2[N:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][N:13]=2)[CH:10]=1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.O>[NH2:1][CH2:4][C:5]1[CH:6]=[C:7]([C:22]2[S:26][C:25]([C@@:27]3([OH:39])[CH2:32][CH2:31][C@H:30]([C:33]([O:35][CH3:36])=[O:34])[C:29]([CH3:37])([CH3:38])[CH2:28]3)=[N:24][CH:23]=2)[CH:8]=[C:9]([NH:11][C:12]2[N:17]=[C:16]([C:18]([F:20])([F:21])[F:19])[CH:15]=[CH:14][N:13]=2)[CH:10]=1

Participants

5

Reactant 2

HCID 11776TriphenylphosphineHCID 86658255HCID 86658255, compound

Product 1

HCID 67432750HCID 67432750, compoundYield 26.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of the product from Step 2 (220 mg, 0.392 mmol) in THF (4 ml) and water (2 ml), was added resin-bound triphenylphosphine (154 mg, 0.588 mmol, 1.5 equiv). The resulting mixture was stirred at 23° C. for 18 h. The resin-bound triphenylphosphine was removed by filtration, and the residual biphasic, orange-maroon mixture was partitioned between EtOAc (45 ml) and water (55 ml). The separated organic layer was dried over Na2SO4, filtered and concentrated. The crude orange oil was purified via reverse-phase HPLC (acetonitrile/water gradient with 0.1% TFA present). The TFA salt was converted to the free base by partitioning between EtOAc (55 ml) and saturated aqueous NaHCO3 (45 ml). The organic layer was dried over Na2SO4, filtered and concentrated. The organic layer was filtered and concentrated, yielding methyl(1S,4R)-4-{5-[3-(aminomethyl)-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl]-1,3-thiazol-2-yl}-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (55 mg, 25%), as an orange oil. MS ESI: [M+H]+ m/z 536.2

Workup

  1. customThe resin-bound triphenylphosphine was removed by filtration
  2. customthe residual biphasic, orange-maroon mixture was partitioned between EtOAc (45 ml) and water (55 ml)
  3. dry with materialThe separated organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude orange oil was purified via reverse-phase HPLC (acetonitrile/water gradient with 0.1% TFA present)
  7. customby partitioning between EtOAc (55 ml) and saturated aqueous NaHCO3 (45 ml)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. filtrationThe organic layer was filtered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-4c04e42c7b484574b047c5f7d1dfd5b9
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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