Citric Acid → HCID 59279471, compound

HRID 1098143Notes

Reaction equation

HRID 1098143 reaction equation
ClC(N(C)C)=C(C)C.[Si:9]([O:16][C@@H:17]([CH2:21][O:22][CH:23]1[CH2:26][CH2:25][CH2:24]1)[C:18]([OH:20])=O)([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10].N1C=CC=CC=1.[CH3:33][C:34]1[CH:35]=[CH:36][C:37]([NH2:40])=[N:38][CH:39]=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][CH:23]1[CH2:26][CH2:25][CH2:24]1)[C:18]([NH:40][C:37]1[CH:36]=[CH:35][C:34]([CH3:33])=[CH:39][N:38]=1)=[O:20])([C:12]([CH3:13])([CH3:14])[CH3:15])([CH3:10])[CH3:11]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 1049PyridineHCID 153482-Amino-5-methylpyridineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 59279488HCID 59279488, compound

Product 1

HCID 59279471HCID 59279471, compoundYield 58.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

1-Chloro-N,N,2-trimethylprop-1-en-1-amine (0.133 mL, 1.00 mmol) was added to a stirred solution of (S)-2-(tert-butyldimethylsilyloxy)-3-cyclobutoxypropanoic acid (Intermediate R4) (250 mg, 0.91 mmol) in DCM (5 mL) at room temperature under nitrogen. The resulting solution was stirred at room temperature for 30 minutes. Pyridine (0.147 mL, 1.82 mmol) was added followed by a solution of 5-methylpyridin-2-amine (108 mg, 1.00 mmol) in DCM (5 mL) and the resulting solution was stirred at ambient temperature for 1 hour. 1M citric acid (10 mL) and DCM (50 mL) were added and the phases were separated. The organic phase washed with water (10 mL) and brine (10 mL), dried (MgSO4), filtered and evaporated. The crude product was purified by flash silica chromatography, eluting with 0 to 30% ethyl acetate in isohexane to afford the product (195 mg, 58.7%). 1H NMR (400 MHz, DMSO) δ 0.01 (d, 6H), 0.80 (s, 9H), 1.24-1.37 (m, 1H), 1.43-1.53 (m, 1H), 1.59-1.72 (m, 2H), 1.94-2.06 (m, 2H), 2.13 (s, 3H), 3.33-3.44 (m, 2H), 3.77-3.87 (m, 1H), 4.29-4.34 (m, 1H), 7.49-7.54 (m, 1H), 7.86 (d, 1H), 8.02-8.06 (m, 1H), 9.25 (s, 1H); m/z (ESI+) (M+H)+=365.47; HPLC tR=3.60 min.

Workup

  1. stirringthe resulting solution was stirred at ambient temperature for 1 hour
  2. customthe phases were separated
  3. washThe organic phase washed with water (10 mL) and brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product was purified by flash silica chromatography
  8. washeluting with 0 to 30% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-e74af7ca11ef434ba6d2c599e434cc41
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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