Dimethylformamide → 6-(Chloromethyl)-2-(methylthio)benzo[d]oxazole

HRID 1848028Notes

Reaction equation

HRID 1848028 reaction equation
[CH3:1][S:2][C:3]1[O:4][C:5]2[CH:11]=[C:10]([CH2:12]O)[CH:9]=[CH:8][C:6]=2[N:7]=1.CN(C=O)C.S(Cl)([Cl:21])=O>C(Cl)Cl>[Cl:21][CH2:12][C:10]1[CH:9]=[CH:8][C:6]2[N:7]=[C:3]([S:2][CH3:1])[O:4][C:5]=2[CH:11]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 866810442-(Methylthio)benzo[d]oxazole-6-methanol

Product 1

HCID 866810166-(Chloromethyl)-2-(methylthio)benzo[d]oxazoleYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2-(methylthio)benzo[d]oxazol-6-yl)methanol (2 g, 10.26 mmol) from Step 2 of this Example in a mixture of anhydrous DMF (0.5 mL) and anhydrous DCM (100 mL) at 0° C. was added dropwise thionyl chloride (4 mL, 55 mmol). The mixture was allowed to warm to rt and stirred for a further 40 min. The mixture was concentrated under reduced pressure and the residue was partitioned between saturated aq NaHCO3 and a 10:1 mixture of DCM:MeOH. The organic layer was separated and dried over MgSO4, filtered, and concentrated under reduced pressure to afford 6-(chloromethyl)-2-(methylthio)benzo[d]oxazole (2 g, 92%) as a light pink solid which did not require further purification. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.75 (d, J=1.3 Hz, 1H), 7.63 (d, J=8.1 Hz, 1H), 7.43 (dd, J=1.3, 8.1 Hz, 1H), 4.89 (s, 2H), 2.77 (s, 3H). LCMS (ESI) m/z 214 (M+H)+.

Workup

  1. customat 0° C.
  2. concentrationThe mixture was concentrated under reduced pressure
  3. customthe residue was partitioned between saturated aq NaHCO3
  4. additiona 10:1 mixture of DCM
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9bd1630df1da4ed3a65c34bf6fa33b1a
Source dataset
uspto-grants-2015_02
Patent number
US08952058B2

Reaction notes

Loading…