Diethyl Ether → HCID 66706896, compound

HRID 2041367Notes

Reaction equation

HRID 2041367 reaction equation
[CH2:1]([Mg]Cl)[C:2]([CH3:5])([CH3:4])[CH3:3].C(OCC)C.[C:13]([O:17][C:18]([N:20]1[CH2:26][CH2:25][C:24]2[C:27]([S:32][CH2:33][C:34]3[CH:39]=[CH:38][C:37](Br)=[CH:36][N:35]=3)=[C:28]([Cl:31])[CH:29]=[CH:30][C:23]=2[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>C1COCC1.CCOC(C)=O.[Cl-].[Zn+2].[Cl-].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:13]([O:17][C:18]([N:20]1[CH2:26][CH2:25][C:24]2[C:27]([S:32][CH2:33][C:34]3[CH:39]=[CH:38][C:37]([CH2:1][C:2]([CH3:5])([CH3:4])[CH3:3])=[CH:36][N:35]=3)=[C:28]([Cl:31])[CH:29]=[CH:30][C:23]=2[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

8

Reactant 3

HCID 3283Diethyl EtherHCID 576562493-tert-butoxycarbonyl-6-(5-bromopyridin-2-ylmethylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 178418809HCID 178418809, compound

Product 1

HCID 66706896HCID 66706896, compoundYield 24%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 53485975CID 53485975CatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 1.0 M neopentyl magnesium chloride in diethyl ether (50 mL, 50 mmol) at −78° C. under nitrogen, add via syringe a solution of 0.5 M zinc chloride in THF (100 mL, 50 mmol). Warm gradually to ambient temperature and transfer via syringe of this solution (25 mL, ˜8.33 mmol) to a stirred solution of 3-tert-butoxycarbonyl-6-(5-bromo-pyridin-2-ylmethylthio)-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (300 mg, 0.62 mmol) in THF (2 mL) at ambient temperature. Add dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (50 mg, 0.061 mmol) and heat at 65° C. for 6 h. 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 (6:1) to give 3-tert-butoxycarbonyl-7-chloro-6-[5-(2,2-dimethyl-propyl)-pyridin-2-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil (69 mg, 24%). MS (APCI+) m/z: 501 (M+H)+. Use a method similar to the General Procedure 1-4 to give the title compound as a white powder. MS (APCI+) m/z: 375 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-5f5e5433befe4ad48fafa1ece81e129c
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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