Water → 2-Chloro-1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]ethanone

HRID 1916442Notes

Reaction equation

HRID 1916442 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH:9]1[O:13][N:12]=[C:11]([C:14]2[N:15]=[C:16]([CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[S:17][CH:18]=2)[CH2:10]1.C(N(CC)C(C)C)(C)C.[Cl:34][CH2:35][C:36](Cl)=[O:37].O>C(Cl)Cl>[Cl:34][CH2:35][C:36]([N:22]1[CH2:23][CH2:24][CH:19]([C:16]2[S:17][CH:18]=[C:14]([C:11]3[CH2:10][CH:9]([C:3]4[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])[O:13][N:12]=3)[N:15]=2)[CH2:20][CH2:21]1)=[O:37]

Participants

6

Reactant 4

HCID 962WaterHCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 666185904‐{4‐[5‐(2,6‐Difluorophenyl)‐4,5‐dihydro‐1,2‐ oxazol‐3‐yl]‐1,3‐thiazol‐2‐yl}piperidine

Product 1

HCID 673742792-Chloro-1-[4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]-1-piperidinyl]ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 4-[4-[5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl]-2-thiazolyl]piperidine (i.e. the product of Example 1, Step D) (4.2 g, 12.0 mmol) and N,N-diisopropylethylamine (1.63 g, 12.6 mmol) in methylene chloride (25 mL) at 0° C. was added a solution of 2-chloroacetyl chloride (1.43 g, 1.26 mmol) in dichloromethane (3 mL), after which time the reaction mixture was allowed to warm to room temperature. After 4 h, the reaction mixture was poured into water and the layers were separated. The organic layer was washed with aqueous hydrochloric acid solution (1 N), saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant) to provide the title compound as a tan solid (2.8 g).

Workup

  1. customthe layers were separated
  2. washThe organic layer was washed with aqueous hydrochloric acid solution (1 N), saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by medium pressure liquid chromatography on silica gel (0 to 100% gradient of ethyl acetate in hexanes as eluant)

Sources & evidence

ORD record
ord-edd28cd100b34c8290b09172cea895c5
Source dataset
uspto-grants-2013_12
Patent number
US08618137B2

Reaction notes

Loading…