Citric Acid → HCID 57504604, compound

HRID 1098118Notes

Reaction equation

HRID 1098118 reaction equation
ClC(N(C)C)=C(C)C.[Si:9]([O:16][C@@H:17]([CH2:21][O:22][CH3:23])[C:18]([OH:20])=O)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].N1C=CC=CC=1.[CH3:30][C:31]1[N:35]=[C:34]([NH2:36])[S:33][N:32]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[Si:9]([O:16][C@@H:17]([CH2:21][O:22][CH3:23])[C:18]([NH:36][C:34]1[S:33][N:32]=[C:31]([CH3:30])[N:35]=1)=[O:20])([C:12]([CH3:13])([CH3:14])[CH3:15])([CH3:10])[CH3:11]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 1049PyridineHCID 3506395-Amino-3-methyl-1,2,4-thiadiazoleHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 57504586HCID 57504586, compound

Product 1

HCID 57504604HCID 57504604, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 1-chloro-N,N,2-trimethylprop-1-en-1-amine (1.521 mL, 11.50 mmol) in DCM (2 mL) was added dropwise to a stirred solution of (S)-2-(tert-butyldimethylsilyloxy)-3-methoxypropanoic acid (Intermediate C4c) (2.45 g, 10.45 mmol) in DCM (10 mL) over a period of 1 minute under nitrogen. The resulting pale yellow solution was stirred at ambient temperature for 30 minutes Anhydrous pyridine (1.262 mL, 15.68 mmol) was added in one portion (solution turns deeper yellow) followed by 3-methyl-1,2,4-thiadiazol-5-amine (CAS no. 17467-35-5) (1.204 g, 10.45 mmol) in DCM (3 mL) dropwise over a period of 1 minute. The resulting solution was stirred at ambient temperature for 1 hour. 1M citric acid (50 mL) added and extracted with EtOAc (50 mL). Organic phase washed with water (25 mL) and brine (25 mL), dried (MgSO4), filtered and evaporated. The residue was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane to afford (S)-2-(tert-butyldimethylsilyloxy)-3-methoxy-N-(3-methyl-1,2,4-thiadiazol-5-yl)propanamide (390 mg, 11%). 1H NMR (400 MHz, CDCl3) δ 0.11 (6H, dd), 0.89 (9H, s), 2.49 (3H, s), 3.30 (3H, s), 3.61 (2H, t), 4.46 (1H, dd), 9.75-9.90 (1H, s); m/z (ESI+) (M+H)+=332.30; HPLC tR=2.77 min.

Workup

  1. additionwas added in one portion (solution turns deeper yellow)
  2. extractionextracted with EtOAc (50 mL)
  3. washOrganic phase washed with water (25 mL) and brine (25 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane

Sources & evidence

ORD record
ord-b9c42af30bde4c1cbea67ddb117154d2
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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