Neopentyl alcohol → HCID 67382309, compound

HRID 911478Notes

Reaction equation

HRID 911478 reaction equation
[CH2:1]([OH:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[H-].[Na+].[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([S:28][CH2:29][C:30]3[N:31]=[N:32][C:33](Cl)=[CH:34][CH:35]=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]>C1COCC1.O>[C:9]([O:13][C:14]([N:16]1[CH2:22][CH2:21][C:20]2[C:23]([S:28][CH2:29][C:30]3[N:31]=[N:32][C:33]([O:6][CH2:1][C:2]([CH3:5])([CH3:4])[CH3:3])=[CH:34][CH:35]=3)=[C:24]([Cl:27])[CH:25]=[CH:26][C:19]=2[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

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 67382309HCID 67382309, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of neopentyl alcohol (105 mg, 1.19 mm ol) 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-23bb5cd9e1a94333a5ff78611eda7037
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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