Oxalyl chloride → HCID 59268022, compound

HRID 1802446Notes

Reaction equation

HRID 1802446 reaction equation
[CH3:1][C:2]([S:7][CH2:8][C@H:9]1[CH2:14][CH2:13][CH2:12][CH2:11][O:10]1)([CH3:6])[C:3]([OH:5])=O.C(Cl)(=O)C(Cl)=O.[C:21]([Si:25]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[O:26][CH2:27][C:28]([C:31]1[S:35][C:34]([NH2:36])=[N:33][N:32]=1)([CH3:30])[CH3:29])([CH3:24])([CH3:23])[CH3:22].C(N(CC)C(C)C)(C)C>CN(C=O)C.C(Cl)Cl.C1(C)C=CC=CC=1>[Si:25]([O:26][CH2:27][C:28]([C:31]1[S:35][C:34]([NH:36][C:3](=[O:5])[C:2]([CH3:1])([S:7][CH2:8][C@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[CH3:6])=[N:33][N:32]=1)([CH3:29])[CH3:30])([C:21]([CH3:22])([CH3:23])[CH3:24])([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 59267851HCID 59267851, compoundHCID 59267899HCID 59267899, compound

Product 1

HCID 59268022HCID 59268022, compoundYield 84.7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

Activation of 300 mg (1.27 mmol) of 2-methyl-2-{[(2R)-oxan-2-ylmethyl]sulfanyl}propanoic acid as the corresponding acid chloride is achieved by treatment with oxalyl chloride (305 mg, 2.54 mmol) and DMF (1 drop) in DCM (10 mL) at room temperature for 18 h. The solvent is removed by distillation, and then azeotroped with toluene (3×5 mL). This acid chloride is dissolved in toluene (5 mL) and added dropwise to a stirred suspension of 565 mg (1.37 mmol) of 5-[2-(tert-butyl-diphenyl-silanyloxy)-1,1-dimethyl-ethyl]-[1,3,4]thiadiazol-2-ylamine and 0.48 mL (2.75 mmol) of N,N-diisopropylethylamine in toluene (10 mL) at room temperature. After complete addition the reaction is heated to 60° C. for 18 h. The reaction is cooled to room temperature and the solvent is removed under reduced pressure. The residue is purified by column chromatography (silica, eluent: heptanes, 0-20% ethyl acetate) to yield 658 mg of N-(5-{1-[(tert-butyldiphenylsilyl)oxy]-2-methylpropan-2-yl}-1,3,4-thiadiazol-2-yl)-2-methyl-2-{[(2R)-oxan-2-ylmethyl]sulfanyl}propanamide. Yield: 73%; m/z 612 [M+H], 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.01-1.09 (9H, m), 1.21-1.70 (17H, m), 1.75-1.84 (1H, m), 2.57-2.72 (2H, m), 3.33 (1H, td, J=11.71, 2.06 Hz), 3.38-3.47 (1H, m), 3.70-3.75 (2H, m), 4.10-4.17 (1H, m), 7.34-7.47 (6H, m), 7.56-7.64 (4H, m), 10.94 (1H, br. s.)

Workup

  1. customThe solvent is removed by distillation
  2. customazeotroped with toluene (3×5 mL)
  3. dissolutionThis acid chloride is dissolved in toluene (5 mL)
  4. additionAfter complete addition the reaction
  5. temperatureThe reaction is cooled to room temperature
  6. customthe solvent is removed under reduced pressure
  7. customThe residue is purified by column chromatography (silica, eluent: heptanes, 0-20% ethyl acetate)

Sources & evidence

ORD record
ord-0e1ee787f6a849b9bab14fcd6ce637af
Source dataset
uspto-grants-2013_01
Patent number
US08349871B2

Reaction notes

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