Tetrahydrofuran → (1S,2R) N-[3-[3-Bromo-5-(2,2-dimethyl-propyl)-benzylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide

HRID 1991536Notes

Reaction equation

HRID 1991536 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][C:3]=1[CH2:4][NH:5][CH2:6][C@@H:7]([OH:22])[C@@H:8]([NH:18][C:19](=[O:21])[CH3:20])[CH2:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=1.BrN(Br)CC1C=CC=CC=1.C1COCC1.[I-].[CH2:44]([Zn+])[C:45]([CH3:48])([CH3:47])[CH3:46]>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].ClCCl>[Br:27][C:24]1[CH:23]=[C:3]([CH:2]=[C:26]([CH2:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH:25]=1)[CH2:4][NH:5][CH2:6][C@@H:7]([OH:22])[C@@H:8]([NH:18][C:19](=[O:21])[CH3:20])[CH2:9][C:10]1[CH:15]=[C:14]([F:16])[CH:13]=[C:12]([F:17])[CH:11]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 86617022dibromobenzylamine (1S,2R)N-[3-(2,5-Dibromo-benzylamino)-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamideHCID 178445888HCID 178445888, compound

Product 1

HCID 58909250(1S,2R) N-[3-[3-Bromo-5-(2,2-dimethyl-propyl)-benzylamino]-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolvent

Procedure

To dibromobenzylamine (1S,2R) N-[3-(2,5-Dibromo-benzylamino)-1-(3,5-difluoro-benzyl)-2-hydroxy-propyl]-acetamide (0.504 g, 1.0 mM, 1 eq) was added 0.5 M THF solution of neopentylzinc iodide (20 mL, 10 eq) and 0.082 g, (0.1 mM, 0.1 eq) of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (Pd(dppf)Cl2 CH2Cl2). A reaction mixture was stirred overnight at room temperature. The reaction was quenched with a saturated aqueous solution of NH4Cl (20 mL) and extracted with ethyl acetate (3×30 mL). Combined organic layers were washed with brine, dried and concentrated.

Workup

  1. customThe reaction was quenched with a saturated aqueous solution of NH4Cl (20 mL)
  2. extractionextracted with ethyl acetate (3×30 mL)
  3. washCombined organic layers were washed with brine
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-81870eeb4a2e4726be7c6fb473e863d5
Source dataset
uspto-grants-2010_01
Patent number
US07645780B2

Reaction notes

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