Tetrahydrofuran → 3-tert-butoxycarbonyl-7-chloro-6-[5-(3-methyl-butyl)-pyridin-2-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041366Notes

Reaction equation

HRID 2041366 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][S:9][C:10]2[C:20]3[CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16][CH2:15][C:14]=3[CH:13]=[CH:12][C:11]=2[Cl:28])=[N:6][CH:7]=1.[Br-].[CH3:30][CH:31]([CH3:35])[CH2:32][CH2:33][Zn+].C1COCC1>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[C:24]([O:23][C:21]([N:17]1[CH2:18][CH2:19][C:20]2[C:10]([S:9][CH2:8][C:5]3[CH:4]=[CH:3][C:2]([CH2:33][CH2:32][CH:31]([CH3:35])[CH3:30])=[CH:7][N:6]=3)=[C:11]([Cl:28])[CH:12]=[CH:13][C:14]=2[CH2:15][CH2:16]1)=[O:22])([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 576562493-tert-butoxycarbonyl-6-(5-bromopyridin-2-ylmethylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 178445882HCID 178445882, compound

Product 1

HCID 667073303-tert-butoxycarbonyl-7-chloro-6-[5-(3-methyl-butyl)-pyridin-2-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 75%

Reagents, catalysts & solvents 1

HCID 53485975CID 53485975Catalyst

Procedure

To 6-(5-bromo-pyridin-2-ylmethylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (219 mg, 0.452 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (18 mg, 0.022 mmol) under dry nitrogen add with stirring a solution of 0.5M 3-methylbutylzinc bromide in THF (4.6 mL, 2.3 mmol). Degas, purge with dry nitrogen, and stir overnight at ambient temperature. Dilute with EtOAc, wash with water, dry over anhydrous MgSO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (5:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[5-(3-methyl-butyl)-pyridin-2-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (160 mg, 75%). MS (APCI+) m/z: 475 (M+H)+. Use a method similar to the General Procedure 1-4 to give the title compound as a tan solid. MS (APCI+) m/z: 375 (M+H)+.

Workup

  1. customDegas
  2. custompurge with dry nitrogen
  3. additionDilute with EtOAc
  4. washwash with water
  5. dry with materialdry over anhydrous MgSO4
  6. concentrationconcentrate in vacuo
  7. customPurify by chromatography on silica gel eluting with hexane/EtOAc (5:1)

Sources & evidence

ORD record
ord-2ccd1c377344475a885b1c4b71981015
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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