1,2-Dichloroethane → 8-Methyl-8-azabicyclo[3.2.1]octan-3-yl 2-phenyl-2-(phenylamino)acetate

HRID 1255007Notes

Reaction equation

HRID 1255007 reaction equation
[C:1]1([CH:7]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:32][N:33]1[CH:38]2[CH2:39][CH2:40][CH:34]1[CH2:35][CH:36](O)[CH2:37]2>CN(C=O)C>[C:1]1([CH:7]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([O:10][CH:36]2[CH2:37][CH:38]3[N:33]([CH3:32])[CH:34]([CH2:40][CH2:39]3)[CH2:35]2)=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 84248-Methyl-8-azabicyclo(3.2.1)octan-3-olHCID 19375alpha-(Phenylamino)benzeneacetic acidHCID 757711-Hydroxybenzotriazole

Product 1

HCID 468412398-Methyl-8-azabicyclo[3.2.1]octan-3-yl 2-phenyl-2-(phenylamino)acetateYield 7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-phenyl-2-(phenylamino)acetic acid I1 (250 mg, 0.90 mmol), EDC (255 mg, 1.35 mmol), HOBt (245 mg, 1.80 mmol) and 8-methyl-8-azabicyclo[3.2.1]octan-3-ol (380 mg, 2.71 mmol) in dry DMF (10 mL) is heated under microwave irradiation at 100° C. for 1 hour (LC-MS monitoring: complete conversion). The reaction is concentrated under reduced pressure and the residue is portioned between EtOAc and water. The organic phase is dried over Na2SO4, filtered and evaporated to dryness. The resulting crude is purified by preparative HPLC. The collected compound is partitioned between 1N NaHCO3 and DCM, the organic phase is separated dried over Na2SO4, filtered and evaporated under vacuum to give 20.1 mg of the title compound as a colorless oil (7% yield, mixture of diastereoisomers).

Workup

  1. concentrationThe reaction is concentrated under reduced pressure
  2. dry with materialThe organic phase is dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe resulting crude is purified by preparative HPLC
  6. customThe collected compound is partitioned between 1N NaHCO3 and DCM
  7. customthe organic phase is separated
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated under vacuum

Sources & evidence

ORD record
ord-d08cad2b28054567aa3577b09df241c2
Source dataset
uspto-grants-2013_06
Patent number
US08455646B2

Reaction notes

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