Monomethyl terephthalate → HCID 67257206, compound

HRID 1476669Notes

Reaction equation

HRID 1476669 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)=[O:4].C(Cl)(=O)C(Cl)=O.Cl.[CH2:21]([O:23][C:24]1[CH:25]=[C:26]([C@@H:32]2[C@H:37]([NH2:38])[CH2:36][CH2:35][S:34][CH2:33]2)[CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH3:22].CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[CH2:21]([O:23][C:24]1[CH:25]=[C:26]([C@@H:32]2[C@H:37]([NH:38][C:9]([C:8]3[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:13][CH:12]=3)=[O:11])[CH2:36][CH2:35][S:34][CH2:33]2)[CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH3:22]

Participants

7

Reactant 4

HCID 15513Monomethyl terephthalateHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 67257610HCID 67257610, compound

Product 1

HCID 67257206HCID 67257206, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent4×

Procedure

To a suspension of 4-(methoxycarbonyl)benzoic acid (11.35 g) in DCM (300 ml) are added 5 drops of DMF and the reaction mixture is stirred for 20 min at RT under a nitrogen atmosphere. To this suspension oxalyl chloride (5.67 ml) dissolved in DCM (60 ml) is slowly added at 0° C. (ice bath The ice bath is removed and the mixture is stirred for 4 h at RT. DCM (3×200 ml) is added to the reaction mixture and the volatiles are co-evaporated under reduced pressure (three times). Finally all volatiles are removed under vacuo to obtain an oil, which is dissolved in DCM (200 ml) and added dropwise to a solution of (3R,4R)-3-(3-ethoxy-4-methoxyphenyl)tetrahydro-2H-thiopyran-4-amine hydrochloride (18.23 g; compound C13) and DIPEA (41.1 ml) in DCM (200 ml) at 0° C. under nitrogen atmosphere. After stirring for 12 h at RT the reaction is quenched by addition of a saturated aqueous solution of sodium hydrogen carbonate. The organic phase is separated, dried over sodium sulfate, filtered and evaporated to dryness in vacuo. The resulting residue is suspended in DIP (300 ml) and heated under reflux for 3.5 h. The suspension is stirred for 2 d at RT and subsequently cooled to 0° (ice bath). The suspension is filtered and the filter cake is washed with little amounts of DIP and dried in vacuo for 12 h at 60° C. to give the title compound as a solid.

Workup

  1. customis removed
  2. stirringthe mixture is stirred for 4 h at RT
  3. additionDCM (3×200 ml) is added to the reaction mixture
  4. customFinally all volatiles are removed under vacuo
  5. customto obtain an oil, which
  6. stirringAfter stirring for 12 h at RT the reaction
  7. customis quenched by addition of a saturated aqueous solution of sodium hydrogen carbonate
  8. customThe organic phase is separated
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated to dryness in vacuo
  12. temperatureheated
  13. temperatureunder reflux for 3.5 h
  14. stirringThe suspension is stirred for 2 d at RT
  15. temperaturesubsequently cooled to 0° (ice bath)
  16. filtrationThe suspension is filtered
  17. washthe filter cake is washed with little amounts of DIP
  18. customdried in vacuo for 12 h at 60° C.

Sources & evidence

ORD record
ord-2a4ea98792974dbd84a1989309594212
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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