Potassium Carbonate → (R)-benzyl 5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate

HRID 42991Notes

Reaction equation

HRID 42991 reaction equation
[CH2:1]([O:8][C:9](=[O:22])[NH:10][C@H:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:20]O)[CH:17]=2)[CH2:12]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[F:33][C:34]([F:43])([F:42])[C:35]1[C:39]([CH2:40][OH:41])=[CH:38][NH:37][N:36]=1>C(Cl)Cl.CN(C=O)C>[OH:41][CH2:40][C:39]1[C:35]([C:34]([F:43])([F:42])[F:33])=[N:36][N:37]([CH2:20][C:16]2[CH:17]=[C:18]3[C:13](=[CH:14][CH:15]=2)[CH2:12][C@@H:11]([NH:10][C:9](=[O:22])[O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH2:19]3)[CH:38]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 70243858(R)-benzyl-5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamateHCID 178519885HCID 178519885, compound

Product 1

HCID 70241273(R)-benzyl 5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-ylcarbamateYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

(R)-benzyl-5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-ylcarbamate (5.08 mmol, 1.51 g) was dissolved in DCM (20 mL), thionyl chloride (10.16 mmol, 0.741 mL, 1.208 g) added and the resultant solution stirred at room temperature for 45 min. The sample was concentrated and azeotroped with DCM (×4). Potassium carbonate (15.23 mmol, 2.105 g) was added followed by DMF (20 mL) and (3-(trifluoromethyl)-1H-pyrazol-4-yl)methanol (5.08 mmol, 0.843 g) and the mixture heated to 60° C. for 1 h. The mixture was concentrated and partitioned between EtOAc/water. The aqueous layer was twice extracted with EtOAc and combined organics dried, filtered and concentrated to give a yellow oil which was purified on silica eluting with 0.5% MeOH/DCM to give (R)-benzyl 5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate as a light coloured oil (1.74 g, 77%). 1H NMR (400 MHz, CDCl3) δ 1.83 (t, 1H) 2.79 (m, 2H) 3.27 (m, 2H) 4.52 (bs, 1H) 4.64 (d, 2H) 4.99 (bs, 1H) 5.09 (bs, 2H) 5.25 (s, 2H) 7.05-7.11 (m, 2H) 7.19 (m, 1H) 7.26-7.40 (m, 6H).

Workup

  1. concentrationThe sample was concentrated
  2. customazeotroped with DCM (×4)
  3. concentrationThe mixture was concentrated
  4. custompartitioned between EtOAc/water
  5. extractionThe aqueous layer was twice extracted with EtOAc
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellow oil which
  9. customwas purified on silica eluting with 0.5% MeOH/DCM

Sources & evidence

ORD record
ord-2e3d3c7a45b6485c89303c71d311ff50
Source dataset
uspto-grants-2013_09
Patent number
US08536214B2

Reaction notes

Loading…