Diethyl 2,2-bis((trifluoromethylsulfonyloxy)methyl)malonate → (R)-diethyl 1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3,3-dicarboxylate

HRID 1809539Notes

Reaction equation

HRID 1809539 reaction equation
[NH2:1][C@H:2]1[C:10]2[C:5](=[C:6]([C:11]3[N:15]=[C:14]([C:16]4[CH:17]=[CH:18][C:19]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=4)[C:21]#[N:22])[O:13][N:12]=3)[CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3]1.FC(F)(F)S(O[CH2:34][C:35]([CH2:46]OS(C(F)(F)F)(=O)=O)([C:41]([O:43][CH2:44][CH3:45])=[O:42])[C:36]([O:38][CH2:39][CH3:40])=[O:37])(=O)=O>CC#N>[C:21]([C:20]1[CH:23]=[C:16]([C:14]2[O:13][N:12]=[C:11]([C:6]3[CH:7]=[CH:8][CH:9]=[C:10]4[C:5]=3[CH2:4][CH2:3][C@H:2]4[N:1]3[CH2:46][C:35]([C:41]([O:43][CH2:44][CH3:45])=[O:42])([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH2:34]3)[N:15]=2)[CH:17]=[CH:18][C:19]=1[O:24][CH:25]([CH3:27])[CH3:26])#[N:22]

Participants

4

Reactant 2

HCID 12073898Diethyl 2,2-bis((trifluoromethylsulfonyloxy)methyl)malonateHCID 58344778(R)-5-(3-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile

Product 1

HCID 67313928(R)-diethyl 1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3,3-dicarboxylateYield 28%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a solution of (R)-5-(3-(1-amino-2,3-dihydro-1H-inden-4-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 49 (247 mg, 0.62 mmol) in CH3CN (2 mL) at −10° C., under N2, was added diethyl 2,2-bis((((trifluoromethyl)sulfonyl)oxy)methyl)malonate INT-26 (3 mL of 0.25 mmol solution in CH3CN). The resulting mixture was warmed to room temperature over 30 min, then heated to 70° C. for 18 h. The mixture was concentrated, dissolved in DCM, and washed with water. The organic layer was dried over Na2SO4 and concentrated to provide 93 mg (28%) of crude (R)-diethyl 1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3,3-dicarboxylate INT-27, which was used in the next step without further purification. LCMS-ESI (m/z) calculated for C30H32N4O6: 544.6; found 545.2 [M+H]+, tR=3.03 min.

Workup

  1. temperatureheated to 70° C. for 18 h
  2. concentrationThe mixture was concentrated
  3. dissolutiondissolved in DCM
  4. washwashed with water
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ce046516d9ee4dc69fae08a7606ed26a
Source dataset
uspto-grants-2013_01
Patent number
US08362048B2

Reaction notes

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