(Bis(2-methoxyethyl)amino)sulfur trifluoride → HCID 90072403, compound

HRID 521940Notes

Reaction equation

HRID 521940 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]2(O)[CH2:11][O:10][CH2:9]2)[CH:5]=[C:4]([F:13])[C:3]=1[C:14]1[S:15][CH:16]=[C:17]([C:19]([O:21][CH3:22])=[O:20])[N:18]=1.COCCN(S(F)(F)[F:33])CCOC>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([C:8]2([F:33])[CH2:11][O:10][CH2:9]2)[CH:5]=[C:4]([F:13])[C:3]=1[C:14]1[S:15][CH:16]=[C:17]([C:19]([O:21][CH3:22])=[O:20])[N:18]=1

Participants

4

Reactant 2

HCID 2734690(Bis(2-methoxyethyl)amino)sulfur trifluorideHCID 90072527HCID 90072527, compound

Product 1

HCID 90072403HCID 90072403, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Following the procedure of Intermediate 104, replacing 2,6-difluoro-4-methoxyphenylboronic acid with 3-(3,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxetan-3-ol (see US2012/225062) gave the title compound, after adding the following fluorination step prior to ester hydrolysis: A solution of methyl 2-(2,6-difluoro-4-(3-hydroxyoxetan-3-yl)phenyl)thiazole-4-carboxylate (50 mg) in dichloromethane (5 mL) was cooled to −78° C., then deoxo-fluor (1.5 equiv., 50 wt % solution in toluene) was added. The mixture was allowed to slowly warm to rt over 30 minutes. The reaction was then quenched by the addition of sat. NaHCO3(aq), then the mixture was diluted with EtOAc and washed with brine. The organic extracts were dried (Na2SO4) and concentrated in vacuo. Purification by CombiFlash (0 to 100% EtOAc in heptane) provided methyl 2-(2,6-difluoro-4-(3-fluorooxetan-3-yl)phenyl)thiazole-4-carboxylate.

Workup

  1. additionafter adding the following fluorination step
  2. customThe reaction was then quenched by the addition of sat. NaHCO3(aq)
  3. additionthe mixture was diluted with EtOAc
  4. washwashed with brine
  5. dry with materialThe organic extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customPurification by CombiFlash (0 to 100% EtOAc in heptane)

Sources & evidence

ORD record
ord-8a8ab00a1e2c4fc7b1aebb13671d1614
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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