Methyl iodide → 3-tert-butoxycarbonyl-7-chloro-6-(4-methoxymethyl-benzylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 911555Notes

Reaction equation

HRID 911555 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:22]3[CH:27]=[CH:26][C:25]([CH2:28][OH:29])=[CH:24][CH:23]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:32]I>CN(C=O)C.O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C:12]2[C:15]([S:20][CH2:21][C:22]3[CH:23]=[CH:24][C:25]([CH2:28][O:29][CH3:32])=[CH:26][CH:27]=3)=[C:16]([Cl:19])[CH:17]=[CH:18][C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 57655963HCID 57655963, compound

Product 1

HCID 667071023-tert-butoxycarbonyl-7-chloro-6-(4-methoxymethyl-benzylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-tert-butoxycarbonyl-7-chloro-6-(4-hydroxymethyl-benzylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (133 mg, 0.306 mmol) in anhydrous DMF (2 mL) under nitrogen, add sodium hydride (60% dispersion, 13-15 mg, 0.375 mmol) at ambient temperature and continue sting for 30 min. Add methyl iodide (80 □L, 1.28 mmol). After 15 min, dilute with water, extract three times with EtOAc, dry over anhydrous MgSO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (15:1) to give 3-tert-butoxycarbonyl-7-chloro-6-(4-methoxymethyl-benzylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a clear oil, which crystallizes on standing to a white solid (87 mg, 63%), along with recovered starting material (22 mg, 17%). Use a method similar to the General Procedure 1-4 to give the title compound as a white solid. MS (ES+) m/z: 348 (M+H−Boc)+.

Workup

  1. waitAfter 15 min
  2. extractionextract three times with EtOAc
  3. dry with materialdry over anhydrous MgSO4
  4. concentrationconcentrate in vacuo
  5. customPurify by chromatography on silica gel eluting with hexane/EtOAc (15:1)

Sources & evidence

ORD record
ord-87cedd92f6e6426bb842daf810bd99bb
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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