Dimethyl Sulfoxide → HCID 23381518, compound

HRID 1280754Notes

Reaction equation

HRID 1280754 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[F:11][C:12]([F:23])([CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:13]O.C(N(CC)CC)C.Br.[NH:32]1[CH2:36][CH2:35][C@H:34]([S:37][C:38]2[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=2)[CH2:33]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.ClCCCl.O>[F:11][C:12]([F:23])([CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:13][N:32]1[CH2:36][CH2:35][C@H:34]([S:37][C:38]2[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=2)[CH2:33]1

Participants

10

Reactant 6

HCID 679Dimethyl SulfoxideHCID 8471Triethylamine2×HCID 65578Oxalyl chlorideHCID 5049666Sodium triacetoxyborohydrideHCID 184257752,2-Difluoro-4-phenylbutan-1-olHCID 69926498HCID 69926498, compound

Product 1

HCID 23381518HCID 23381518, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent3×

Procedure

To a −60° C. solution of oxalylchloride (0.21 ml, 2.42 mmol) in dry CH2Cl2 (4 ml) was added a solution of DMSO (0.34 ml, 4.84 mmol) in CH2Cl2 (2 ml). After 5 minutes stirring, a solution of 2,2-difluoro-4-phenyl-butan-1-ol (0.41 g, 2.2 mmol) in CH2Cl2 was added dropwise at −60° C. After 15 minutes stirring, triethylamine (1.54 ml, 11 mmol) was added dropwise, the reaction mixture was allowed to warm up to room temperature and H2O (10 ml) was added. The aqueous phase was extracted with CH2Cl2 (3×20 ml).The combined organic phases were dried over Na2SO4, filtered and the solvent was removed in vacuo. The residue was dissolved in 1,2-dichloroethane (15 ml) and added to a suspension of (3S)-4-(pyrrolidin-3-ylsulfanyl)-phenol hydrobromide (0.68 g, 2.2 mmol), triethylamine (0.31 ml, 2.2 mmol) and sodium triacetoxyborohydride (0.74 g, 3.30 mmol) in 1,2-dichloroethane (45 ml). Mixture was stirred at 65° C. for 2 hours and overnight at room temperature. H2O (30 ml) was added. The aqueous phase was extracted with CH2Cl2 (3×20 ml).The combined organic phases were dried over Na2SO4, filtered and the solvent was removed in vacuo. The residue was chromatographed over silica gel (hexane-ethylacetate 99:1 to 90:10) to provide (3S)-4-[1-(2,2-difluoro-4-phenyl-butyl)-pyrrolidin-3-ylsulfanyl]-phenol (0.55 g, 70%) as light yellow oil, MS: m/e=364.2(M+H+).

Workup

  1. stirringAfter 15 minutes stirring
  2. extractionThe aqueous phase was extracted with CH2Cl2 (3×20 ml).The combined organic phases
  3. dry with materialwere dried over Na2SO4
  4. filtrationfiltered
  5. customthe solvent was removed in vacuo
  6. dissolutionThe residue was dissolved in 1,2-dichloroethane (15 ml)
  7. stirringMixture was stirred at 65° C. for 2 hours and overnight at room temperature
  8. extractionThe aqueous phase was extracted with CH2Cl2 (3×20 ml).The combined organic phases
  9. dry with materialwere dried over Na2SO4
  10. filtrationfiltered
  11. customthe solvent was removed in vacuo
  12. customThe residue was chromatographed over silica gel (hexane-ethylacetate 99:1 to 90:10)

Sources & evidence

ORD record
ord-31f9519742a949d39d695e8d05510844
Source dataset
uspto-grants-2002_09
Patent number
US06451819B2

Reaction notes

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