Sodium hydride → HCID 67335991, compound

HRID 1670559Notes

Reaction equation

HRID 1670559 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][SH:8].[H-].[Na+].[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22]2[C:25]([CH2:30]Cl)=[C:26]([Cl:29])[CH:27]=[CH:28][C:21]=2[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]>CN(C=O)C.O>[C:11]([O:15][C:16]([N:18]1[CH2:24][CH2:23][C:22]2[C:25]([CH2:30][S:8][CH2:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[C:26]([Cl:29])[CH:27]=[CH:28][C:21]=2[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 2560712-PyridinemethanethiolHCID 597874103-tert-Butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 67335991HCID 67335991, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

Evaporate a solution of 2-pyridine methanethiol (2.5 mL, 10% in EtOH) in vacuo to obtain neat 2-pyridine methanethiol (250 mg). Immediately dissolve 2-pyridine methanethiol (230 mg, 1.84 mmol) in anhydrous DMF (5 mL) under an atmosphere of nitrogen. Add sodium hydride (100 mg, 2.5 mmol, 60% dispersion in mineral oil) and stir for 10 min. Add a solution of 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (550 mg, 1.67 mmol) in anhydrous DMF (1 mL) and stir under nitrogen for 2 h. Quench reaction by slow addition of water (10 mL), dilute up to 150 mL with water and extract with DCM (3×50 mL). Wash the combined organic extracts with brine, dry over Na2SO4, filter and concentrate in vacuo. Purify by chromatography on silica gel (40 g) eluting with hexane/EtOAc (9:1 to 1:1 gradient over 60 min, 40 mL/min) to obtain 3-tert-butoxycarbonyl-7-chloro-6-(pyridin-2-ylmethylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (275 mg, 40%) as a light yellow syrup.

Workup

  1. customQuench
  2. customreaction
  3. extractionextract with DCM (3×50 mL)
  4. washWash the combined organic extracts with brine
  5. dry with materialdry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate in vacuo
  8. customPurify by chromatography on silica gel (40 g)
  9. washeluting with hexane/EtOAc (9:1 to 1:1 gradient over 60 min, 40 mL/min)

Sources & evidence

ORD record
ord-af46f71719014f3c926c9dd5560fbd18
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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