Iodoethane → (+/-)-3-tert-butoxycarbonyl-7-chloro-6-(1-cyanopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 2041411Notes

Reaction equation

HRID 2041411 reaction equation
[CH:1]([N-]C(C)C)(C)[CH3:2].[Li+].C1CCCCC1.[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][C:26]2[C:29]([S:34][CH2:35][C:36]#[N:37])=[C:30]([Cl:33])[CH:31]=[CH:32][C:25]=2[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(I)C>C1COCC1>[C:15]([O:19][C:20]([N:22]1[CH2:28][CH2:27][C:26]2[C:29]([S:34][CH:35]([C:36]#[N:37])[CH2:1][CH3:2])=[C:30]([Cl:33])[CH:31]=[CH:32][C:25]=2[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 6340IodoethaneHCID 8078CyclohexaneHCID 2724682Lithium diisopropylamideHCID 667072373-tert-butoxycarbonyl-7-chloro-6-(1-cyano-methylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 66706966(+/-)-3-tert-butoxycarbonyl-7-chloro-6-(1-cyanopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a stirred solution of 1.5M lithium diisopropylamide in cyclohexane (1.37 mL, 2.05 mmol) in dry THF (5 mL) at −78° C. under dry nitrogen, add a solution of 3-tert-butoxycarbonyl-7-chloro-6-cyanomethylthio-2,3,4,5-tetrahydro-1H-benzo[d]-azepine (600 mg, 1.70 mmol) in THF (5 mL) and continue stirring for 2 h. Rapidly transfer the above solution via cannula to a solution of ethyl iodide (13.2 g, 84.9 mmol) in THF (5 mL) and continue stirring for 1 h. Quench with aqueous saturated ammonium chloride solution, extract three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (9:1) to give (±)-3-tert-butoxycarbonyl-7-chloro-6-(1-cyanopropylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a pale oil (350 mg, 68%). Use a method similar to the General Procedure 1-4 to give the title compound as an off-white solid. MS (ES+) m/z: 281 (M+H)+.

Workup

  1. stirringcontinue stirring for 1 h
  2. customQuench with aqueous saturated ammonium chloride solution
  3. extractionextract three times with EtOAc
  4. dry with materialdry over anhydrous Na2SO4
  5. concentrationconcentrate in vacuo
  6. customPurify by chromatography on silica gel eluting with hexane/EtOAc (9:1)

Sources & evidence

ORD record
ord-45989a00a2fd4545aca9d9c6e81e46f7
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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