4-(2-Oxiranylmethoxy)benzenecarbonitrile → Tert-butyl 3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3-azabicyclo-[3.2.1]oct-8-yl(methyl)carbamate

HRID 411520Notes

Reaction equation

HRID 411520 reaction equation
[CH:1]12[CH:8]([N:9]([CH3:17])[C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:5]([CH2:6][CH2:7]1)[CH2:4][NH:3][CH2:2]2.C[Al](C)C.[O:22]1[CH2:24][CH:23]1[CH2:25][O:26][C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=1>ClCCl>[C:31]([C:30]1[CH:33]=[CH:34][C:27]([O:26][CH2:25][CH:23]([OH:22])[CH2:24][N:3]2[CH2:4][CH:5]3[CH:8]([N:9]([CH3:17])[C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:14])[CH3:15])[CH:1]([CH2:7][CH2:6]3)[CH2:2]2)=[CH:28][CH:29]=1)#[N:32]

Participants

5

Reactant 3

HCID 27643014-(2-Oxiranylmethoxy)benzenecarbonitrileHCID 16682925TrimethylaluminumHCID 18541001Tert-butyl 3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate

Product 1

HCID 18540975Tert-butyl 3-[3-(4-cyanophenoxy)-2-hydroxypropyl]-3-azabicyclo-[3.2.1]oct-8-yl(methyl)carbamateYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of tert-butyl 3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate (Preparation D; 1.68 g, 7.0 mmol) in dichloromethane (35 mL) at 25° C. under nitrogen was added trimethylaluminum (3.75 mL of 2.0 M in hexanes, 7.0 mmol). After stirring at 25° C. for 30 min, 4-(2-oxiranyl-methoxy)benzonitrile (Preparation E(i); 1.22 g, 7.0 mmol) was added in one portion, and the mixture was stirred overnight. The mixture was quenched with 3 N NaOH (11.5 mL) and stirred for 1 h. Water (30 mL) was added, and the aqueous layer was extracted with dichloromethane (3×30 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford an oil. The residue was chromatographed on silica gel, eluting with dichloromethane:methanol (98:2), to afford 2.35 g (81%) of the subtitle compound as a white solid.

Workup

  1. stirringthe mixture was stirred overnight
  2. customThe mixture was quenched with 3 N NaOH (11.5 mL)
  3. stirringstirred for 1 h
  4. additionWater (30 mL) was added
  5. extractionthe aqueous layer was extracted with dichloromethane (3×30 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford an oil
  10. customThe residue was chromatographed on silica gel
  11. washeluting with dichloromethane:methanol (98:2)

Sources & evidence

ORD record
ord-46ed3642345845818ef5a4267015ecac
Source dataset
uspto-grants-2003_05
Patent number
US06559162B2

Reaction notes

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