Citric Acid → HCID 57504587, compound

HRID 1098103Notes

Reaction equation

HRID 1098103 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].C(N(C(C)C)C(C)C)C.[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][CH3:23])[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 153482-Amino-5-methylpyridineHCID 81531DiisopropylethylamineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 57504586HCID 57504586, compound

Product 1

HCID 57504587HCID 57504587, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of 1-chloro-N,N,2-trimethylprop-1-en-1-amine (1.55 mL, 11.7 mmol) in DCM (5 mL) was added dropwise to a stirred solution of (S)-2-(tert-butyldimethylsilyloxy)-3-methoxypropanoic acid C4c (2.5 g, 10.7 mmol) in DCM (15 mL) under nitrogen. The resulting solution was stirred at ambient temperature for 30 minutes. N-Ethyl-N-isopropylpropan-2-amine (2.74 mL, 16.0 mmol) was added in one portion followed by 5-methylpyridin-2-amine (CAS 1603-41-4) (1.27 g, 11.73 mmol) in DCM (5 mL) dropwise. The resulting solution was stirred at ambient temperature for 1 hour. 1M Citric acid (10 mL) was added and the mixture extracted with EtOAc (20 mL). The organic phase was washed with water (5 mL) and brine (5 mL), dried over MgSO4, filtered and evaporated to provide the crude product. Purification by flash silica chromatography, elution gradient 20 to 100% EtOAc in isohexane furnished (S)-2-(tert-butyldimethylsilyloxy)-3-methoxy-N-(5-methylpyridin-2-yl)propanamide (1.4 g). 1H NMR (400 MHz, CDCl3) δ 0.2 (6H, s), 1.01 (9H, s), 2.32 (3H, s), 3.41 (3H, s), 3.66-3.75 (2H, m), 4.40-4.42 (1H, m), 7.52 (1H, d), 7.14-7.16 (2H, m), 9.04 (1H, s), m/z (ESI+) (M+H)+=326; HPLC tR=2.75 min.

Workup

  1. stirringThe resulting solution was stirred at ambient temperature for 1 hour
  2. extractionthe mixture extracted with EtOAc (20 mL)
  3. washThe organic phase was washed with water (5 mL) and brine (5 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customto provide the crude product
  8. customPurification
  9. washby flash silica chromatography, elution gradient 20 to 100% EtOAc in isohexane

Sources & evidence

ORD record
ord-d817530b901249ac86048afbe8aacc91
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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