Ammonia → Benzyl 3-({[(tert-butoxy)carbonyl]amino}methyl)-3-hydroxyazetidine-1-carboxylate

HRID 1672903Notes

Reaction equation

HRID 1672903 reaction equation
[O:1]1[C:3]2([CH2:6][N:5]([C:7]([O:9][CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:8])[CH2:4]2)[CH2:2]1.[NH3:17].[C:18]([O:22][C:23]([O:25]C(OC(C)(C)C)=O)=O)([CH3:21])([CH3:20])[CH3:19]>C1COCC1>[CH3:19][C:18]([O:22][C:23]([NH:17][CH2:2][C:3]1([OH:1])[CH2:6][N:5]([C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])[CH2:4]1)=[O:25])([CH3:21])[CH3:20]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 90495Di-tert-butyl dicarbonateHCID 594692221-Oxa-5-azaspiro[2.3]hexane-5-carboxylic acid phenylmethyl ester

Product 1

HCID 67051555Benzyl 3-({[(tert-butoxy)carbonyl]amino}methyl)-3-hydroxyazetidine-1-carboxylateYield 7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Phenylmethyl 1-oxa-5-azaspiro[2.3]hexane-5-carboxylate (165 mg, 0.75 mmol), prepared using procedures similar to those described in Reference 3, in THF (1 mL) was added to anhydrous ammonia saturated in THF (10 mL) and the mixture was allowed to stir in a sealed vessel at room temperature over 24 hours. The solution was then concentrated and taken back into THF (1 mL) followed by addition of di-tert-butyldicarbonate (164 mg, 0.75 mmol) and stirred for one hour at room temperature. The mixture was then concentrated and the residue purified by silica gel flash chromatography using hexanes:ethyl acetate (1:1) as eluent to give phenylmethyl 3-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]-3-hydroxyazetidine-1-carboxylate (16.5 mg, 7% yield) and unreacted epoxide (120 mg, 73% recovery). 1H-NMR (400 MHz, CDCl3): 7.34 (m, 5H), 5.10 (br, 1H), 5.09 (s, 2H), 4.68 (s, 1H), 3.90 (dd AB, 4H), 3.41 (d, 2H), 1.44 (s, 9H).

Workup

  1. concentrationThe solution was then concentrated
  2. stirringstirred for one hour at room temperature
  3. concentrationThe mixture was then concentrated
  4. customthe residue purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-ee304b984f734994b757db42c649571e
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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