Diethylamine → HCID 57852690, compound

HRID 1506720Notes

Reaction equation

HRID 1506720 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[S:5][CH:4]([C:12]([OH:14])=O)[CH2:3]1.C(Cl)(=O)C(Cl)=O.[CH2:21]([NH:23][CH2:24][CH3:25])[CH3:22].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.CN(C=O)C>[CH2:21]([N:23]([CH2:24][CH3:25])[C:12]([CH:4]1[CH2:3][C:2](=[O:1])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[S:5]1)=[O:14])[CH3:22]

Participants

7

Reactant 4

HCID 8021DiethylamineHCID 11430Potassium CarbonateHCID 65578Oxalyl chlorideHCID 11839188HCID 11839188, compound

Product 1

HCID 57852690HCID 57852690, compoundYield 65.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

(+−)-4-Oxo-thiochroman-2-carboxylic acid (10.4 g, 50 mmol), prepared as described in T. Okubo et al (Bioorg. Med. Chem. 2004; 12: 3569-3580), in dry DCM (100 ml) was stirred under an atmosphere of nitrogen at room temperature with oxalyl chloride (12.6 g, 100 mmole) and one drop of DMF for 18 h. The reaction was then evaporated in vacuo to a gum and then redissolved in DCM (100 ml), cooled to 0° C. on an ice bath, stirred and treated dropwise with diethylamine (8.03 g, 110 mmol) in DCM (20 ml) over a period of 1 h. The reaction was allowed to warm to room temperature over 1 h and 10% aqueous potassium carbonate solution (100 ml) was added and the reaction mixture vigorously stirred. The DCM solution was separated. The aqueous solution was extracted with two further batches of DCM (100 ml) and the combined extracts were dried over magnesium sulphate. The DCM solution was concentrated in vacuo to give a dark green oil that crystallized on standing. The crystalline solid was triturated with diethyl ether (50 ml) and filtered to give the title compound (50) (8.57 g, 65%) as a pale green solid. The structure was confirmed by 1H NMR (300 MHz, CDCl3) δ 1.06 (t, J=7.1 Hz, 3H), 1.23 (t, J=7.1 Hz, 3H), 3.0-3.5 (m, 6H), 4.25 (m, 1H), 7.15-7.21 (m, 2H), 7.32-7.39 (m, 1H), 8.10-8.14 (m, 1H).

Workup

  1. customThe reaction was then evaporated in vacuo to a gum
  2. dissolutionredissolved in DCM (100 ml)
  3. temperatureto warm to room temperature over 1 h
  4. stirringthe reaction mixture vigorously stirred
  5. customThe DCM solution was separated
  6. extractionThe aqueous solution was extracted with two further batches of DCM (100 ml)
  7. dry with materialthe combined extracts were dried over magnesium sulphate
  8. concentrationThe DCM solution was concentrated in vacuo
  9. customto give a dark green oil that
  10. customcrystallized
  11. customThe crystalline solid was triturated with diethyl ether (50 ml)
  12. filtrationfiltered

Sources & evidence

ORD record
ord-20bbd271a578484dbaf1a48ba43ac65d
Source dataset
uspto-grants-2015_12
Patent number
US09220795B2

Reaction notes

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