Water → Tert-butyl 3-(3-chloro-5-(1-chloroethyl)-2-fluoro-6-methoxyphenyl)azetidine-1-carboxylate

HRID 1499688Notes

Reaction equation

HRID 1499688 reaction equation
N1C(Cl)=NC(Cl)=NC=1[Cl:3].CN(C)C=O.[Cl:15][C:16]1[C:17]([F: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>ClCCl>[Cl:15][C:16]1[C:17]([F: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 86666860Tert-butyl 3-(3-chloro-2-fluoro-5-(1-hydroxyethyl)-6-methoxyphenyl)azetidine-1-carboxylate

Product 1

HCID 86666861Tert-butyl 3-(3-chloro-5-(1-chloroethyl)-2-fluoro-6-methoxyphenyl)azetidine-1-carboxylateYield 53.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Cyanuric chloride (140 mg, 0.78 mmol) was added to N,N-dimethylformamide (0.059 mL, 0.77 mmol) at room temperature. After the formation of a white solid (ca. 10 minutes), methylene chloride (4 mL) was added, followed by tert-butyl 3-[3-chloro-2-fluoro-5-(1-hydroxyethyl)-6-methoxyphenyl]azetidine-1-carboxylate (197 mg, 0.547 mmol). After addition, the mixture was stirred at room temperature overnight. Water was added, and then diluted with dichloromethane. The organic phases were washed with sat. NaHCO3 solution, water and brine, dried over MgSO4, and concentrated. The resulting residue was purified on silica gel (eluting with 0 to 30% EtOAc in hexanes) to give the desired product (110 mg, 53%).

Workup

  1. additionAfter addition
  2. washThe organic phases were washed with sat. NaHCO3 solution, water and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customThe resulting residue was purified on silica gel (eluting with 0 to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-914ea672d1064a7bb41e318c8f06182d
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

Loading…