Dimethyl Sulfide → 2-(Benzyloxy)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(chloromethyl)-6-methylpyridine

HRID 577445Notes

Reaction equation

HRID 577445 reaction equation
C1C(=O)N([Cl:8])C(=O)C1.CSC.[CH2:12]([O:19][C:20]1[C:25]([CH2:26]O)=[C:24]([CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH:23]=[C:22]([CH3:37])[N:21]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>C(Cl)Cl>[CH2:12]([O:19][C:20]1[C:25]([CH2:26][Cl:8])=[C:24]([CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[CH:23]=[C:22]([CH3:37])[N:21]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 1068Dimethyl SulfideHCID 31398ChlorosuccinimideHCID 86723682[2-(Benzyloxy)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-6-methylpyridin-3-yl]methanol

Product 1

HCID 867236832-(Benzyloxy)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-(chloromethyl)-6-methylpyridineYield 65.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-40 °C

Procedure

To a 0° C. solution of NCS (70.2 mg, 0.515 mmol) in DCM (2 mL) was added DMS (34.9 mg, 0.562 mmol). The reaction mixture was cooled to −40° C., then a solution of [2-(benzyloxy)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-6-methylpyridin-3-yl]methanol (Cpd J, 175 mg, 0.468 mmol) in DCM (1 mL) was added drop-wise keeping the internal temperature below −30° C. Upon complete addition the reaction mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was washed with brine, dried with MgSO4, filtered, then concentrated under vacuum. The residue was purified by column chromatography (0-30% EtOAc/heptane) to give the title compound (Cpd K, 120 mg, 65%) as an oil. 1H NMR (400 MHz, chloroform-d) δ 7.50 (d, J=7.3 Hz, 2H), 7.44-7.29 (m, 3H), 6.94 (s, 1H), 5.46 (s, 2H), 4.83 (s, 2H), 4.70 (s, 2H), 2.47 (s, 3H), 0.97 (s, 9H), 0.14 (s, 6H); MS 392 [M+H].

Workup

  1. customthe internal temperature below −30° C
  2. additionUpon complete addition the reaction mixture
  3. temperaturewas warmed to room temperature
  4. washThe reaction mixture was washed with brine
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by column chromatography (0-30% EtOAc/heptane)

Sources & evidence

ORD record
ord-23611815b5d44d369db3f80e35f11439
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

Loading…