Dichloromethane → HCID 86296662, compound

HRID 513952Notes

Reaction equation

HRID 513952 reaction equation
Cl[C:2]1[C:11]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:10][C:9]2[C:4](=[CH:5][C:6]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)=[CH:7][CH:8]=2)[N:3]=1.ClCCl.CN(C)CCN(C)C.[BH4-].[Na+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl.ClCCl>[Cl:26][C:22]1[CH:21]=[C:20]([CH:25]=[CH:24][CH:23]=1)[CH2:19][O:18][C:6]1[CH:5]=[C:4]2[C:9]([CH:10]=[C:11]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH:2]=[N:3]2)=[CH:8][CH:7]=1

Participants

10

Reactant 4

HCID 6344DichloromethaneHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 4311764Sodium borohydride2×HCID 90417116Ethyl 2-(2-chloro-7-((3-chlorobenzyl)oxy)quinolin-3-yl)acetate

Product 1

HCID 86296662HCID 86296662, compoundYield 55%

Reagents, catalysts & solvents 5

HCID 6344DichloromethaneCatalystHCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Procedure

A solution of ethyl 2-(2-chloro-7-((3-chlorobenzyl)oxy)quinolin-3-yl)acetate (5 g, 12.8 mmol) in THF (50 mL) was degassed with nitrogen for 5 minutes and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1.36 g, 1.67 mmol) was added, followed by N1,N1,N2,N2-tetramethylethane-1,2-diamine (3.84 mL, 25.6 mmol) and sodium tetrahydroborate (969 mg, 25.6 mmol). The resulting solution was stirred at ambient temperature. After 4 h an additional portion of 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (50 mg, 0.06 mmol) and sodium tetrahydroborate (969 mg, 25.6 mmol) were added and stirred overnight. The reaction was quenched into sat. aqueous NH4Cl and extracted with EtOAc (3×30 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to afford a brown oil. Purification (FCC, SiO2, 0-60%, EtOAc/hexanes) afforded the title compound as a colorless oil (2.5 g, 55%) that crystallized upon standing. 1H NMR (400 MHz, CDCl3) 8.76 (d, J=2.3 Hz, 1H), 8.02 (s, 1H), 7.71 (d, J=9.0 Hz, 1H), 7.52-7.43 (m, 2H), 7.32 (dd, J=6.5, 12.7 Hz, 4H), 5.19 (s, 2H), 4.18 (q, J=7.0 Hz, 2H), 3.77 (s, 2H), 1.26 (t, J=7.0 Hz, 3H). [M+H]=356.2.

Workup

  1. stirringstirred overnight
  2. customThe reaction was quenched into sat. aqueous NH4Cl
  3. extractionextracted with EtOAc (3×30 mL)
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customto afford a brown oil
  7. customPurification (FCC, SiO2, 0-60%, EtOAc/hexanes)

Sources & evidence

ORD record
ord-c8d5ad3101bd4f36a07e31a7e6977258
Source dataset
uspto-grants-2015_08
Patent number
US09102674B2

Reaction notes

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