Tetrahydrofuran → HCID 67112059, compound

HRID 1177464Notes

Reaction equation

HRID 1177464 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:26](=[O:28])[CH3:27])[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:19][CH2:18]1)[N:11]=2.[CH3:29][Mg]Cl.C1COCC1>C(OCC)C.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:26]([OH:28])([CH3:29])[CH3:27])[CH:5]=[CH:6][C:7]=1[C:8]1[S:9][C:10]2[C:15]([N:16]=1)=[CH:14][CH:13]=[C:12]([C:17]1([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[CH2:18][CH2:19]1)[N:11]=2

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 59174916HCID 59174916, compoundHCID 178418332HCID 178418332, compound

Product 1

HCID 67112059HCID 67112059, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

To 1-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)ethanone (0.732 g, 1.88 mmol) in diethyl ether (15.7 mL) and toluene (14.7 mL) at 0° C. under argon was added methylmagnesium chloride, 3.0 M solution in THF (1.38 mL, 4.14 mmol). After stirring at 0° C. for 10 minutes, the reaction mixture was allowed to warm to room temperature and stirred for another 1 hour. The reaction mixture was quenched with saturated NH4Cl solution and diluted with CH2Cl2; the aqueous layer was back-extracted with CH2Cl2. The combined organic extracts were dried (MgSO4), filtered, and concentrated in vacuo. ISCO purification with 10% to 30% EtOAc/Hexanes afforded 2-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridine-2-yl)phenyl)propan-2-ol as a colorless foam. MS (ESI) m/z: Calculated: 404.1; Observed: 405.1 (M++1).

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for another 1 hour
  3. customThe reaction mixture was quenched with saturated NH4Cl solution
  4. additiondiluted with CH2Cl2
  5. extractionthe aqueous layer was back-extracted with CH2Cl2
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customISCO purification with 10% to 30% EtOAc/Hexanes

Sources & evidence

ORD record
ord-49153c40c6c5431e8114fb67d231dbff
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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