Pyridine → (R,R)-N-[3-(4-hydroxyphenyl)-4-methylisothiazol-5-yl]-2-methylcyclopropanecarboxamide

HRID 2422704

Reaction equation

HRID 2422704 reaction equation
C(Cl)(=O)C(Cl)=O.ClCCl.[CH3:10][C@@H:11]1[CH2:13][C@H:12]1[C:14]([OH:16])=O.[NH2:17][C:18]1[S:22][N:21]=[C:20]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)[C:19]=1[CH3:30].N1C=CC=CC=1>CN(C=O)C.C1(C)C=CC=CC=1.C1COCC1.CCOC(C)=O>[OH:29][C:26]1[CH:25]=[CH:24][C:23]([C:20]2[C:19]([CH3:30])=[C:18]([NH:17][C:14]([C@@H:12]3[CH2:13][C@H:11]3[CH3:10])=[O:16])[S:22][N:21]=2)=[CH:28][CH:27]=1

Participants

10

Reactant 5

HCID 1049PyridineHCID 6344DichloromethaneHCID 65578Oxalyl chlorideHCID 6995705rel-(1R,2R)-2-Methylcyclopropanecarboxylic acidHCID 1363552854-(5-Amino-4-methylisothiazol-3-yl)phenol

Product 1

HCID 136244237(R,R)-N-[3-(4-hydroxyphenyl)-4-methylisothiazol-5-yl]-2-methylcyclopropanecarboxamideYield 64.6%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Add oxalyl chloride (2 M in dichloromethane, (0.291 mL, 0.583 mmol) to a stirred solution of (R,R)-2-methylcyclopropanecarboxylic acid (0.06 g, 0.58 mmol) and DMF (1 drop-catalytic) in toluene (1 mL). Stir 3 h and add the now formed acid chloride to a stirred solution of 4-(5-amino-4-methylisothiazol-3-yl)phenol (0.060 g, 0.291 mmol) and pyridine (0.07 g, 0.87 mmol) in THF (1 mL). Stir 1 h and dilute with EtOAc (300 mL), and wash with 1 N NaOH (2 times 100 mL) then water (100 mL), dry (MgSO4) and evaporate. Crystallize from chloroform and hexane. Yield: 64.6%. ES-MS: m/e 289.0 (m+1).

Workup

  1. stirringStir 1 h
  2. washwash with 1 N NaOH (2 times 100 mL)
  3. dry with materialwater (100 mL), dry (MgSO4)
  4. customevaporate
  5. customCrystallize from chloroform and hexane

Sources & evidence

ORD record
ord-ad34b95702754957aa30c7779bafce6d
Source dataset
uspto-grants-2011_06
Patent number
US07960419B2

Linked notes

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