Hydrogen Bromide → HCID 86717584, compound

HRID 715518Notes

Reaction equation

HRID 715518 reaction equation
C([O:8][CH2:9][C:10]1([CH2:21][N:22]2[C:26]3[CH:27]=[C:28]([C:31]#[N:32])[CH:29]=[CH:30][C:25]=3[N:24]=[CH:23]2)[CH2:20][CH2:19][CH2:18][C:12]2([O:16][C:15](=[O:17])[NH:14][CH2:13]2)[CH2:11]1)C1C=CC=CC=1.Br.[OH-].[Na+]>O1CCOCC1>[OH:8][CH2:9][C@:10]1([CH2:21][N:22]2[C:26]3[CH:27]=[C:28]([C:31]#[N:32])[CH:29]=[CH:30][C:25]=3[N:24]=[CH:23]2)[CH2:20][CH2:19][CH2:18][C@:12]2([O:16][C:15](=[O:17])[NH:14][CH2:13]2)[CH2:11]1

Participants

5

Reactant 3

HCID 260Hydrogen BromideHCID 14798Sodium HydroxideHCID 71227140HCID 71227140, compound

Product 1

HCID 86717584HCID 86717584, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a light orange suspension of 1-((7-((benzyloxy)methyl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (0.120 g, 0.279 mmol) in 1,4-dioxane (2.157 mL) was added concentrated hydrobromic acid (0.631 mL, 5.57 mmol). The reaction mixture was heated at 70° C. for 17 h. The reaction was then cooled to RT. Next, 6N NaOH was added till the pH was adjusted to 13 and then the mixture extracted with EtOAc (2×10 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated. The compound was loaded onto florisil and purified using silica gel chromatography: 1-5% methanol/dichloromethane (25 min), 4 g silica. The product eluted early from 2-10 minutes. Next, the compound was loaded onto florisil and purified using silica gel chromatography: 1-10% methanol/dichloromethane (30 min), 12 g silica. The product did not elute cleanly but did yield 1-{[(5S,7R)-7-(hydroxymethyl)-2-oxo-1-oxa-3-azaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile (70% pure, 62 mg, 46% yield). MS (m/z) 341.0 (M+H+).

Workup

  1. temperatureThe reaction was then cooled to RT
  2. extractionthe mixture extracted with EtOAc (2×10 mL)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified
  7. custom1-5% methanol/dichloromethane (25 min), 4 g silica
  8. washThe product eluted early from 2-10 minutes
  9. custompurified
  10. custom1-10% methanol/dichloromethane (30 min), 12 g silica
  11. washThe product did not elute cleanly

Sources & evidence

ORD record
ord-5ef70dc56d9e40b79e216a7ea963a0f2
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

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