Water → tert-Butyl 3-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]azetidine-1-carboxylate

HRID 1499671Notes

Reaction equation

HRID 1499671 reaction equation
N1C(Cl)=NC(Cl)=NC=1[Cl:3].CN(C)C=O.[Cl:15][C:16]1[C:17]([CH3:38])=[C:18]([CH:27]2[CH2:30][N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:28]2)[C:19]([O:25][CH3:26])=[C:20]([CH:22](O)[CH3:23])[CH:21]=1.O>C(Cl)Cl>[Cl:15][C:16]1[C:17]([CH3:38])=[C:18]([CH:27]2[CH2:30][N:29]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:28]2)[C:19]([O:25][CH3:26])=[C:20]([CH:22]([Cl:3])[CH3:23])[CH:21]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 7954Cyanuric chlorideHCID 86677626tert-Butyl 3-[3-chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]azetidine-1-carboxylate

Product 1

HCID 86677627tert-Butyl 3-[3-chloro-5-(1-chloroethyl)-6-methoxy-2-methylphenyl]azetidine-1-carboxylateYield 86.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Cyanuric chloride (from Aldrich, 1.22 g, 6.62 mmol) was weighed into a flask and N,N-dimethylformamide (0.512 mL, 6.62 mmol) was added. After stirring for a few minutes a solution of tert-butyl 3-[3-chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]azetidine-1-carboxylate (1.5 g, 4.2 mmol) in methylene chloride (30 mL) was added. The resulting mixture was stirred at room temperature overnight. Water was added, and then diluted with dichloromethane. The layers were separated and the organics were washed with sat. NaHCO3 solution, water, brine, dried over MgSO4, and concentrated. The resulting residue was purified on silica gel, eluting with 0-35% EtOAc in hexanes to give the desired product (1.36 g, 86%). LCMS calculated for C13H17ClNO (M—Cl—Boc+H)+: m/z=238.1; Found: 238.1. 1H NMR (400 MHz, CDCl3): δ 7.46 (s, 1H), 5.44, (q, 1H), 4.32 (m, 2H), 4.18-4.10 (m, 3H), 3.67 (s, 3H), 2.27 (s, 3H), 1.79 (d, 3H), 1.44 (s, 9H) ppm.

Workup

  1. additionwas added
  2. customThe layers were separated
  3. washthe organics were washed with sat. NaHCO3 solution, water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe resulting residue was purified on silica gel
  7. washeluting with 0-35% EtOAc in hexanes

Sources & evidence

ORD record
ord-ff150aeb96114bc68c77859d591f75c7
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

Loading…