Hydrochloric Acid → HCID 67466031, compound

HRID 540362Notes

Reaction equation

HRID 540362 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=O)[CH2:3][CH2:2]1.[Br:10][C:11]1[CH:20]=[C:19]2[C:14]([CH2:15][CH2:16][N:17](C=O)[CH2:18]2)=[CH:13][CH:12]=1.[B-](F)(F)(F)F.CN(C(ON1C(=O)C=CC=C1)=[N+](C)C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)C(C)C)C.Cl>C(Cl)Cl.CCOCC>[Br:10][C:11]1[CH:20]=[C:19]2[C:14]([CH2:15][CH2:16][N:17]([C:7]([CH:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)=[O:9])[CH2:18]2)=[CH:13][CH:12]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 219302Oxane-4-carboxylic acidHCID 2733204O-(2-Oxo-1(2H)-pyridyl)-N,N,N',N'-tetramethyluronium TetrafluoroborateHCID 735546127-Bromo-3,4-dihydroisoquinoline-2(1H)-carbaldehyde

Product 1

HCID 67466031HCID 67466031, compoundYield 108%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of tetrahydropyran-4-carboxylic acid 130 mg (1 mmol) in DCM (5 mL) was added 7-bromo-3,4-dihydro-1H-isoquinoline-2-carbaldehyde (200 mg, 1 mmol), followed by TPTU (326 mg) and HOBt (148 mg). The solution was cooled to ice-water bath. To this solution was added ethyl diisopropylamine (0.4 mL). The yellow solution was allowed to stir under nitrogen overnight. LC/MS showed the reaction was complete. The reaction was quenched by addition of sodium bicarbonate solution (5 mL) and DCM (30 mL). The two layers were separated, and the aqueous layer was extracted with DCM (20 mL×2). The combined DCM extracts were washed with sodium bicarbonate (20 mL), and brine (15 mL×2), dried (anhydrous potassium carbonate), filtered, and concentrated in vacuo. The crude product was purified on a silica gel column, eluted with 5-10% MeOH in DCM to get a yellow semi-solid. This was taken in DCM and ether (5 mL) and treated with 0.5 mL of 1N HCl in ether. The white powder was collected and dried to get 0.35 g (100% yield) of the titled compound as a yellow solid.

Workup

  1. temperatureThe solution was cooled to ice-water bath
  2. customThe reaction was quenched by addition of sodium bicarbonate solution (5 mL) and DCM (30 mL)
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with DCM (20 mL×2)
  5. washThe combined DCM extracts were washed with sodium bicarbonate (20 mL), and brine (15 mL×2)
  6. dry with materialdried (anhydrous potassium carbonate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified on a silica gel column
  10. washeluted with 5-10% MeOH in DCM
  11. customto get a yellow semi-solid
  12. customThe white powder was collected
  13. customdried

Sources & evidence

ORD record
ord-ad50b77f45414ba893b7f74afb7fac82
Source dataset
uspto-grants-2014_10
Patent number
US08871788B2

Reaction notes

Loading…