Sodium Carbonate → HCID 89649297, compound

HRID 1773936Notes

Reaction equation

HRID 1773936 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[C:14](B3OC(C)(C)C(C)(C)O3)[CH:15]=[CH:16][C:17]=2[F:21])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:33][C:34](=[O:46])[CH:35]([C:37]1[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[C:39](Br)[CH:38]=1)[CH3:36])C.C(=O)([O-])[O-].[Na+].[Na+].O.[OH-].[Li+]>C1(C)C=CC=CC=1.CO.O.C(Cl)Cl.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(O)=O>[CH2:1]([O:8][C:9]([N:11]1[CH2:20][CH2:19][C:18]2[C:13](=[C:14]([C:41]3[CH:42]=[C:37]([CH:35]([C:34]([OH:46])=[O:33])[CH3:36])[CH:38]=[CH:39][C:40]=3[O:43][CH3:44])[CH:15]=[CH:16][C:17]=2[F:21])[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 168937Lithium hydroxide, monohydrateHCID 574588042-(3-Bromo-4-methoxy-phenyl)-propionic acid ethyl esterHCID 896488855-fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester

Product 1

HCID 89649297HCID 89649297, compound

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 284Formic AcidSolventHCID 6344DichloromethaneSolventHCID 70394911HCID 70394911, compoundSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture under N2 of 5-fluoro-8-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (82 mg, 0.20 mmol, 1.00 eq.), (±)-2-(3-bromo-4-methoxy-phenyl)-propionic acid ethyl ester (63 mg, 0.20 mmol, 1.00 eq.) and sodium carbonate (85 mg, 0.80 mmol, 4.00 eq.) in toluene/MeOH/water 20:4:1 (4 mL), tetrakis(triphenylphosphine) palladium (0) (12 mg, 0.01 mmol, 0.05 eq.) was added and the mixture was stirred at 100° C. for 18 hours. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was partitioned between AcOEt (10 mL) and water (10 mL). The layers were separated. The org. phase was washed with sat. aq. NaCl soln. (1×5 mL), dried over MgSO4 and filtered through Celite. The filtrate was concentrated in vacuo. To a solution of the previous residue in DMF (0.9 mL), 1M aq. NaOH soln. (1.3 mL) was added. The mixture was stirred at 50° C. for 18 hours. The reaction mixture was concentrated in vacuo. The residue was redissolved in THF (2 mL) and water (2 mL). Lithiumhydroxide monohydrate (23 mg, 0.54 mmol, 2.71 eq.) was added and the mixture was stirred at 50° C. for 18 hours. Formic acid was added (0.2 mL). The solution was diluted with DCM. The layers were separated and the aq. phase was extracted with DCM (2×). The comb. org. layers were dried over MgSO4, filtered and concentrated in vacuo.

Workup

  1. temperatureto cool to r.t.
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between AcOEt (10 mL) and water (10 mL)
  4. customThe layers were separated
  5. washphase was washed with sat. aq. NaCl soln
  6. dry with material(1×5 mL), dried over MgSO4
  7. filtrationfiltered through Celite
  8. concentrationThe filtrate was concentrated in vacuo
  9. addition(1.3 mL) was added
  10. stirringThe mixture was stirred at 50° C. for 18 hours
  11. concentrationThe reaction mixture was concentrated in vacuo
  12. dissolutionThe residue was redissolved in THF (2 mL)
  13. stirringthe mixture was stirred at 50° C. for 18 hours
  14. customThe layers were separated
  15. extractionthe aq. phase was extracted with DCM (2×)
  16. dry with materiallayers were dried over MgSO4
  17. filtrationfiltered
  18. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9a35d2a01478439eb5af8b217dc51ca9
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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