Neopentyl alcohol → 2,3,4,5-Tetrahydro-1H-benzo(d)azepine

HRID 2041354Notes

Reaction equation

HRID 2041354 reaction equation
C(O)C(C)(C)C.[H-].[Na+].C(OC([N:16]1[CH2:22][CH2:21][C:20]2[C:23](SCC3N=NC(Cl)=CC=3)=[C:24](Cl)[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=O)(C)(C)C>C1COCC1.O>[CH2:21]1[C:20]2[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17][NH:16][CH2:22]1

Participants

6

Reactant 3

HCID 6404Neopentyl alcoholHCID 24758Sodium hydrideHCID 866296553-tert-butoxycarbonyl-7-chloro-6-(6-chloro-pyridazin-3-ylmethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 14002432,3,4,5-Tetrahydro-1H-benzo(d)azepineYield 93.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of neopentyl alcohol (105 mg, 1.19 mmol) in THF (5 mL) at ambient temperature add sodium hydride (31 mg, 95%, 1.19 mmol) and continue stirring for 3 h at ambient temperature. Add a solution of 3-tert-butoxycarbonyl-7-chloro-6-(6-chloro-pyridazin-3-ylmethylthio)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (315 mg, 0.59 mmol) in THF (1 mL) and continue stirring overnight at ambient temperature and then at 60° C. for 1 h. Dilute with water, extract the reaction mixture three times with EtOAc, dry over anhydrous Na2SO4, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (6:1) to give 3-tert-butoxycarbonyl-7-chloro-6,6-(2,2-dimethyl-propoxy)-pyridazin-3-ylmethylthio]-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a clear oil (81 mg, 28%). MS (APCI+) m/z: 492 (M+H)+, 392 (M+H-Boc)+. Use a method similar to the General Procedure 1-4 to give the title compound as a white powder. MS (APCI+) m/z: 392 (M+H)+, m/z: 322 (M+H—C5H11)+.

Workup

  1. stirringcontinue stirring overnight at ambient temperature
  2. waitat 60° C. for 1 h
  3. extractionextract the reaction mixture 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 (6:1)

Sources & evidence

ORD record
ord-c61c3fcc520c47c7b999cebc4984a5d2
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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