Acetic Acid → HCID 68182975, compound

HRID 1615550Notes

Reaction equation

HRID 1615550 reaction equation
CC(C)([O-])C.[K+].[C:7]([C:9]1[C:10]([CH2:25][C:26]2[CH:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=2)=[C:11]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[S:12][C:13]=1[N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)#[N:8].Br[CH2:37][N:38]1[C:42](=[O:43])[C:41]2=[CH:44][CH:45]=[CH:46][CH:47]=[C:40]2[C:39]1=[O:48].C(O)(=O)C>CN(C)C=O.O>[C:7]([C:9]1[C:10]([CH:25]([C:26]2[CH:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=2)[CH2:37][N:38]2[C:42](=[O:43])[C:41]3[C:40](=[CH:47][CH:46]=[CH:45][CH:44]=3)[C:39]2=[O:48])=[C:11]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[S:12][C:13]=1[N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)#[N:8]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 792441H-Isoindole-1,3(2H)-dione, 2-(bromomethyl)-HCID 23665647Potassium tert-butoxideHCID 66747680HCID 66747680, compound

Product 1

HCID 68182975HCID 68182975, compoundYield 45.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent3×

Conditions

Temperature
-50 °C

Procedure

A dry 40 mL vial charged with a mixture of potassium tert-butoxide (0.110 g, 0.984 mmol) in anhydrous N,N-dimethylformamide (2.0 mL) was cooled to −50° C. with an acetonitrile-dry ice bath under nitrogen. To the vial was added a suspension of ethyl 4-cyano-5-morpholin-4-yl-3-(2-naphthylmethyl)thiophene-2-carboxylate (0.200 g, 0.492 mmol) in anhydrous N,N-dimethylformamide (2.0 mL) dropwise. After 10 min of stirring the resulting black solution, a solution of N-bromomethylphthalimide (0.142 g, 0.590 mmol) in anhydrous N,N-dimethylformamide (1.0 mL) was added dropwise and the mixture was stirred at −52° C.˜−45° C. for 90 min. The reaction was quenched with acetic acid (0.084 mL, 1.5 mmol) and warmed up to r.t. The solution was diluted with water (˜30 mL), and the resulting pale yellow solid was collected by filtration. The crude solid was dissolved in DCM (30 mL), washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. Purification on a silica gel column (continuous gradient of EtOAc/hexane 0˜50%) afforded the title product (0.126 g, yield 45.3%). LCMS: (FA) ES+ 566. 1H NMR (400 MHz, d-chloroform) δ: 7.95 (s, 1H), 7.90-7.75 (m, 5H), 7.73-7.63 (m, 2H), 7.50-7.40 (m, 3H), 6.03 (m, 1H), 4.87-4.73 (m, 2H), 4.20-4.10 (m, 2H), 3.82-3.75 (m, 4H), 3.51-3.42 (m, 4H), 1.20-1.13 (m, 3H).

Workup

  1. additionTo the vial was added
  2. stirringthe mixture was stirred at −52° C.˜−45° C. for 90 min
  3. temperaturewarmed up to r.t
  4. filtrationthe resulting pale yellow solid was collected by filtration
  5. dissolutionThe crude solid was dissolved in DCM (30 mL)
  6. washwashed with brine
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification on a silica gel column (continuous gradient of EtOAc/hexane 0˜50%)

Sources & evidence

ORD record
ord-17aa06f79ac14e6d9a8481fbf4da9daa
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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