Tetrahydrofuran → 3-tert-butoxycarbonyl-7-chloro-6-[3-fluoro-4-(3-methylbutyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041388Notes

Reaction equation

HRID 2041388 reaction equation
Br[C:2]1[CH:28]=[CH:27][C:5]([CH2:6][S:7][C:8]2[C:18]3[CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14][CH2:13][C:12]=3[CH:11]=[CH:10][C:9]=2[Cl:26])=[CH:4][C:3]=1[F:29].[Br-].[CH3:31][CH:32]([CH3:36])[CH2:33][CH2:34][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:22]([O:21][C:19]([N:15]1[CH2:16][CH2:17][C:18]2[C:8]([S:7][CH2:6][C:5]3[CH:27]=[CH:28][C:2]([CH2:34][CH2:33][CH:32]([CH3:36])[CH3:31])=[C:3]([F:29])[CH:4]=3)=[C:9]([Cl:26])[CH:10]=[CH:11][C:12]=2[CH2:13][CH2:14]1)=[O:20])([CH3:25])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 576562686-(4-bromo-3-fluorobenzylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 178445882HCID 178445882, compound

Product 1

HCID 667065573-tert-butoxycarbonyl-7-chloro-6-[3-fluoro-4-(3-methylbutyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 42%

Reagents, catalysts & solvents 1

HCID 53485975CID 53485975Catalyst

Conditions

Temperature
80 °C

Procedure

To 6-(4-bromo-3-fluorobenzylthio)-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.210 mg, 0.42 mmol) and dichloro[1,1′-bis(diphenylphosphino)-ferrocene]palladium(II) dichloromethane adduct (17 mg, 0.021 mmol) add 0.5 M 3-methylbutylzinc bromide in THF (4.2 mL, 2.10 mmol). Degas, purge with dry nitrogen, and stir overnight at 80° C. Cool to 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 (9:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[3-fluoro-4-(3-methylbutyl)-benzylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a yellow oil (85 mg, 42%). Use a method similar to the General Procedure 1-4 to give the title compound as a white solid. MS (ES+) m/z: 392 (M+H)+.

Workup

  1. customDegas
  2. custompurge with dry nitrogen
  3. temperatureCool to ambient temperature
  4. additiondilute with EtOAc
  5. washwash with water
  6. dry with materialdry over anhydrous MgSO4
  7. concentrationconcentrate in vacuo
  8. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

Sources & evidence

ORD record
ord-41def21ae59444a4bd3b7f8d7fcd7bd5
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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