Lithium hydroxide, monohydrate → HCID 67335805, compound

HRID 1670573Notes

Reaction equation

HRID 1670573 reaction equation
O.[OH-].[Li+].[C:4]([S:7][C:8]1[N:9]=[C:10]([CH3:20])[N:11](C(OC(C)(C)C)=O)[CH:12]=1)(=O)[CH3:5].BrCC1[C:33]2[CH2:32][CH2:31][N:30]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:29][CH2:28][C:27]=2[CH:26]=[CH:25][C:24]=1[Cl:41]>CO>[C:37]([O:36][C:34]([N:30]1[CH2:31][CH2:32][C:33]2[C:5]([CH2:4][S:7][C:8]3[NH:9][C:10]([CH3:20])=[N:11][CH:12]=3)=[C:24]([Cl:41])[CH:25]=[CH:26][C:27]=2[CH2:28][CH2:29]1)=[O:35])([CH3:40])([CH3:39])[CH3:38]

Participants

5

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 59787403HCID 59787403, compoundHCID 59822297HCID 59822297, compound

Product 1

HCID 67335805HCID 67335805, compoundYield 77.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Add lithium hydroxide hydrate (42 mg, 1 mmol) to a stirred solution of 4-acetylsulfanyl-1-tert-butoxycarbonyl-2-methyl-imidazole (290 mg, 1.13 mmol) and 6-bromomethyl-3-tert-butoxycarbonyl-7-chloro-2,3,4,5-tetrahydro-1H-benzo[d]azepine (368 mg, 0.98 mmol) in methanol (12 mL) and stir the resulting mixture for 30 min. Partition the mixture between EtOAc and water and extract the aqueous phase three times with EtOAc. Dry the combined organic extracts over MgSO4, filter, and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel (40 g) eluting with hexane/EtOAc [100:0 (5 min), 19:1 (5 min), 85:15 (5 min), 4:1; flow rate: 50 mL/min] to give 3-tert-butoxycarbonyl-7-chloro-6-(2-methyl-3H-imidazol-4-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (310 mg, 54%). MS (ES+) m/z: 508 (M+H)+.

Workup

  1. customPartition the mixture between EtOAc and water
  2. extractionextract the aqueous phase three times with EtOAc
  3. dry with materialDry the combined organic extracts over MgSO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify the crude mixture by chromatography on silica gel (40 g)
  7. washeluting with hexane/EtOAc [100:0 (5 min), 19:1 (5 min), 85:15 (5 min), 4:1; flow rate: 50 mL/min]

Sources & evidence

ORD record
ord-36266461b42c432a8c2f594c9ba373ff
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

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