Sodium hydride → HCID 67337074, compound

HRID 1670560Notes

Reaction equation

HRID 1670560 reaction equation
[SH:1][C:2]1[S:3][CH2:4][CH2:5][N:6]=1.[H-].[Na+].[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([CH2:28]Cl)=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>CN(C=O)C>[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([CH2:28][S:1][C:2]3[S:3][CH2:4][CH2:5][N:6]=3)=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 597874103-tert-Butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepineHCID 178527880HCID 178527880, compound

Product 1

HCID 67337074HCID 67337074, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 2-mercaptothiazoline (0.3 g, 2.5 mmol) in anhydrous DMF (8.5 mL) at room temperature add sodium hydride (0.1 g, 2.6 mmol, 60% dispersion in mineral oil) in portions. After stirring at room temperature for 10 min, add a solution of 3-tert-butoxycarbonyl-7-chloro-6-chloromethyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.74 g, 2.3 mmol) in anhydrous DMF (5.6 mL). Stir at room temperature overnight and quench the reaction mixture with 10% aqueous NaHCO3 (14 mL). Extract the mixture twice with EtOAc. Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM, load the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 95:5 hexane/EtOAc over 30 min; 95:5 hexane/EtOAc over 3 min; 95:5 to 75:25 hexane/EtOAc over 30 min; 75:25 hexane/EtOAc over 3 min; 35 mL/min) to afford 3-tert-butoxycarbonyl-7-chloro-6-(4,5-dihydro-thiazol-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.77 g, 83%). MS (ES+) m/z: 413.1 (M+H)+.

Workup

  1. stirringStir at room temperature overnight
  2. customquench the reaction mixture with 10% aqueous NaHCO3 (14 mL)
  3. extractionExtract the mixture twice with EtOAc
  4. dry with materialDry the combined organic extracts over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. dissolutionDissolve the residue in DCM
  8. customload the solution on to a RediSep® column (40 g) and purify the crude mixture by preparative liquid chromatography (100:0 to 95:5 hexane/EtOAc over 30 min; 95:5 hexane/EtOAc over 3 min; 95:5 to 75:25 hexane/EtOAc over 30 min; 75:25 hexane/EtOAc over 3 min; 35 mL/min)

Sources & evidence

ORD record
ord-cfb66af4c74440e4b554d4e3d7ceceb0
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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