Potassium Carbonate → Tert-butyl 7-[4-(4-cyanophenyl)butyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate

HRID 1351132Notes

Reaction equation

HRID 1351132 reaction equation
C1(C)C(S(O[CH2:11][CH2:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=2)(=O)=O)=CC=CC=1.Cl.[CH:25]12[O:33][CH:29]([CH2:30][NH:31][CH2:32]1)[CH2:28][N:27]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:26]2.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[C:21]([C:18]1[CH:17]=[CH:16][C:15]([CH2:14][CH2:13][CH2:12][CH2:11][N:31]2[CH2:32][CH:25]3[O:33][CH:29]([CH2:28][N:27]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:26]3)[CH2:30]2)=[CH:20][CH:19]=1)#[N:22]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 18540411Tert-butyl 9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate hydrochlorideHCID 865936554-(4-Cyanophenyl)butyl toluenesulphonate

Product 1

HCID 18540378Tert-butyl 7-[4-(4-cyanophenyl)butyl]-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A 2 L three-necked flask was equipped with a magnetic stirrer, a thermometer and a reflux condenser. The flask was charged with a solution of 4-(4-cyanophenyl)butyl toluenesulphonate (72 g, 0.218 mol, see step (iii) above) in dimethylformamide (0.55 L). tert-Butyl 9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylate hydrochloride (48.2, 0.182 mol, see Preparation B(I)(iv) above) was added, followed by potassium carbonate (62.9 g, 0.455 mol). The heterogeneous mixture was stirred for 22 hours at 85° C. TLC analysis indicated complete consumption of starting material. The reaction mixture was cooled to room temperature and diluted with water (0.5 L). The mixture was extracted with ethyl acetate (3×0.4 L) and the organic fractions were combined. After washing with Water (2×200 mL) and brine (200 mL), the organic layer was dried with magnesium sulfate, filtered and concentrated under vacuum. The crude brown oil was purified by chromatography on silica gel, eluting with 3:2 hexanes/ethyl acetate affording 34 g (48% yield) of sub-title compound as an off-white solid.

Workup

  1. customA 2 L three-necked flask was equipped with a magnetic stirrer
  2. customconsumption of starting material
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with water (0.5 L)
  5. extractionThe mixture was extracted with ethyl acetate (3×0.4 L)
  6. washAfter washing with Water (2×200 mL) and brine (200 mL)
  7. dry with materialthe organic layer was dried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum
  10. customThe crude brown oil was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-c5599b5fec8343d483fe9fd390a148bb
Source dataset
uspto-grants-2007_05
Patent number
US07217708B2

Reaction notes

Loading…