Formaldehyde → (+/-)-methyl (3aR,5S,6aR)-2-(phenylmethyl)hexahydro-2H-cyclopenta[d]isoxazole-5-carboxylate

HRID 1820681Notes

Reaction equation

HRID 1820681 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH:8]=[CH:7][CH2:6]1)=[O:4].C=O.Cl.[OH:13][NH:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[CH2:22](N(CC)CC)C>C1(C)C=CC=CC=1.CCO>[C:16]1([CH2:15][N:14]2[CH2:22][C@H:7]3[CH2:6][C@H:5]([C:3]([O:2][CH3:1])=[O:4])[CH2:9][C@H:8]3[O:13]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8471TriethylamineHCID 1514118Methyl cyclopent-3-ene-1-carboxylateHCID 11332622N-benzylhydroxylamine hydrochloride

Product 1

HCID 57891805(+/-)-methyl (3aR,5S,6aR)-2-(phenylmethyl)hexahydro-2H-cyclopenta[d]isoxazole-5-carboxylateYield 85%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

To a solution of methyl-3-cyclopentene-1-carboxylate (6.1 g, 48.4 mmole) in toluene (150 mL) and EtOH (75 mL) was added paraformaldehyde (10.6 g, 242 mmole), N-hydroxybenzylamine hydrochloride (11.4 g, 72.6 mmole) and triethylamine (10.1 mL, 72.6 mmole). After 24 hours at 80° C., the reaction solution was concentrated under vacuum and redissolved in hexanes/EtOAc, 4:1 (200 mL) and filtered. The organic solution was concentrated and then purified on silica (hexanes/EtOAc, 4:1) to give the title compound (10.7 g, 85%) as a light yellow oil containing mixture of diastereoisomers in the ratio of 6 (trans) to 1 (cis): LC-MS (ES) m/e 262 (M+H)+.

Workup

  1. concentrationthe reaction solution was concentrated under vacuum
  2. dissolutionredissolved in hexanes/EtOAc
  3. filtration4:1 (200 mL) and filtered
  4. concentrationThe organic solution was concentrated
  5. custompurified on silica (hexanes/EtOAc, 4:1)

Sources & evidence

ORD record
ord-4ed86a1c8b2345e6946ccdc34b0f15e4
Source dataset
uspto-grants-2009_10
Patent number
US07605169B2

Reaction notes

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