Hydrochloric Acid → HCID 9954095, compound

HRID 1872591Notes

Reaction equation

HRID 1872591 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9][C:10]1[CH:20]=[CH:19][CH:18]=[CH:17][C:11]=1/[CH:12]=[CH:13]/[C:14]([OH:16])=O.C(Cl)(C(Cl)=O)=O.[NH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][OH:34].CCN(C(C)C)C(C)C.Cl>C(Cl)Cl.CN(C=O)C.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9][C:10]1[CH:20]=[CH:19][CH:18]=[CH:17][C:11]=1/[CH:12]=[CH:13]/[C:14]([NH:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][OH:34])=[O:16]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 199606-Amino-1-hexanolHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 10496253HCID 10496253, compound

Product 1

HCID 9954095HCID 9954095, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A suspension of the acid (284 mg, 0.87 mmol) from Example 1B in 5 mL of methylene chloride was stirred with (COCl)2 (84 μL, 0.97 mmol), and one drop of DMF under nitrogen atmosphere for 90 minutes. The solvent was then removed under vacuum. The residue (COCl)2 was removed with benzene (2×) in vacuo. To a separate flask, previously filled with 6-amino-1-hexanol (12 mg, 0.10 mmol), Hunig's base (22.8 μL, 0.13 mmol) and DMAP (1.1 mg, 0.008 mmol) in 2.0 mL of CH2Cl2, the acid chloride (30 mg, 0.087 mmol) in 1.0 mL of CH2Cl2 was then dropped in slowly. After 30 minutes, the reaction mixture was poured into 3N HCl and extracted with ethyl aceetate (EtOAc). The organic layer was washed with brine, dried with Na2SO4, condensed under reduced pressure. The crude product was purified by preparative TLC to give 21.0 mg (90%) of the title compound as a colorless oil. 1H NMR (CDCl3, 300 MHz) δ 1.31-1.48 (m, 4H), 1.48-1.70 (m, 4H), 3.37 (q, J=6.7 Hz, 2H), 3.65 (t, J=6.3 Hz, 2H), 5.63 (br s, 1H), 6.36 (d, J=15.9 Hz, 1H), 6.71 (d, J=9.3 Hz, 1H), 7.05 (dd, J=2.4, 8.7 Hz, 1H), 7.31-7.49 (m, 4H), 7.65 (dd, J=2.1, 7.5 Hz, 1H), 7.99 (d, J=15.9 Hz, 1H). MS (DCI/NH3) (M+NH4)+ at m/z 441, 443, 445.

Workup

  1. customThe solvent was then removed under vacuum
  2. customThe residue (COCl)2 was removed with benzene (2×) in vacuo
  3. extractionextracted with ethyl aceetate (EtOAc)
  4. washThe organic layer was washed with brine
  5. dry with materialdried with Na2SO4, condensed under reduced pressure
  6. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-9b459722306347758016731cbff28a15
Source dataset
uspto-grants-2000_08
Patent number
US06110922

Reaction notes

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