Sulfuric Acid → 1-(Diphenylmethyl)-3-hydroxyazetidine-3-carboxamide

HRID 1672897Notes

Reaction equation

HRID 1672897 reaction equation
[C:1]1([CH:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:8]2[CH2:11][C:10]([O:14][Si](C)(C)C)([C:12]#[N:13])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(=O)(=O)(O)[OH:26].[OH-].[NH4+]>ClCCl>[C:1]1([CH:7]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:8]2[CH2:11][C:10]([OH:14])([C:12]([NH2:13])=[O:26])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 14923Ammonium HydroxideHCID 579892141-(Diphenylmethyl)-3-[(trimethylsilyl)oxy]azetidine-3-carbonitrile

Product 1

HCID 596518481-(Diphenylmethyl)-3-hydroxyazetidine-3-carboxamideYield 76%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-(Diphenylmethyl)azetidin-3-one (600 mg, 2.53 mmol), was dissolved in dichloromethane (1 mL) and treated with triethylamine (0.5 mL, 3.59 mmol) and trimethylsilylcyanide (0.8 mL, 6.01 mmol) at ambient for 2 h and then the mixture was concentrated in vacuo to afford 1-(diphenylmethyl)-3-[(trimethylsilyl)oxy]azetidine-3-carbonitrile (774 mg, 2.30 mmol, 91% yield) as a yellow solid. 1-(diphenylmethyl)-3-[(trimethylsilyl)oxy]azetidine-3-carbonitrile (250 mg, 0.744 mmol) was dissolved in dichloromethane (2 mL) at 0° C. and concentrated sulfuric acid (0.2 mL) was added dropwise. The mixture was stirred at ambient for 2 h and then was cooled to 0° C. and 25% ammonium hydroxide solution was added carefully dropwise to pH ˜10-11. The mixture was extracted twice with dichloromethane. The combined organic portion was washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a residue which was triturated with hexanes/ether to afford 1-(diphenylmethyl)-3-hydroxyazetidine-3-carboxamide (160 mg, 0.567 mmol, 76% yield) as an off-white solid: 1H NMR (400 MHz, CDCl3): 7.92 (br s, 1H), 7.39-7.34 (m, 4H), 7.33-7.27 (m, 4H), 7.27-7.19 (m, 2H), 5.61 (br s, 1H), 4.45 (s, 1H), 4.34 (s, 1H), 3.50 (dd, 2H), 3.20 (dd, 2H); MS (EI) for C17H18N2O2: 283 (MH+).

Workup

  1. extractionThe mixture was extracted twice with dichloromethane
  2. washThe combined organic portion was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford a residue which
  7. customwas triturated with hexanes/ether

Sources & evidence

ORD record
ord-5820dff119394217a35295cfab8cc087
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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