Acetonitrile → HCID 16038977, compound

HRID 2252418Notes

Reaction equation

HRID 2252418 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@H:11]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([OH:24])[CH:19]=4)=[CH:14][CH:13]=3)[C@@H:10]([CH2:25][CH2:26][C@@H:27]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[OH:28])[C:9]2=[O:36])=[CH:4][CH:3]=1.[Br-:37].[Br-].[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.C([N+](CCCC)(CCCC)CCCC)CCC.S([O-])([O-])(=O)=S.[Na+].[Na+].C(#N)C>C(Cl)(Cl)Cl.O>[Br:37][C:23]1[CH:22]=[CH:21][C:20]([OH:24])=[CH:19][C:18]=1[C:15]1[CH:14]=[CH:13][C:12]([C@H:11]2[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[C:9](=[O:36])[C@@H:10]2[CH2:25][CH2:26][C@@H:27]([C:29]2[CH:30]=[CH:31][C:32]([F:35])=[CH:33][CH:34]=2)[OH:28])=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 24477Sodium ThiosulfateHCID 16039224HCID 16039224, compoundHCID 23500184Tetra-n-butylammonium tribromide

Product 1

HCID 16038977HCID 16038977, compoundYield 35.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

(3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(3′-hydroxybiphenyl-4-yl)azetidin-2-one (19.2 mg, 0.04 mmol) was dissolved in chloroform (0.4 mL) and tetrabutylammonium tribromide (18.8 mg, 0.04 mmol) was added at room temperature. After 10 minutes, saturated aqueous sodium thiosulfate (2 mL) was added to quench the reaction. The mixture was poured into a seperatory funnel, extracted with dichloromethane (4×10 mL), dried over sodium sulfate, filtered and concentrated. (3R,4S)-4-(2′-bromo-5′-hydroxybiphenyl-4-yl)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one was purified by chromatography (12 g silica gel, 5% to 95% ethyl acetate-hexane) and then by reverse-phase HPLC (21 mm column, 50% to 100% acetonitrile-0.1% trifluoroacetic acid in water) to afford (3R,4S)-4-(2′-bromo-5′-hydroxybiphenyl-4-yl)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one (8.0 mg, 34% yield) as a clear foam; Rf 0.51 (50% ethyl acetate-hexane); 1H NMR (300 MHz, CDCl3) δ 7.49 (d, J=8.7 Hz, 1H), 7.40 (m, 4H), 7.29 (m, 4H), 7.02 (t, J=8.7 Hz, 2H), 6.95 (t, J=8.7 Hz, 2H), 6.80 (d, J=3.3, 1H), 6.73 (dd, J=3.0, 3.0 Hz, 1H), 4.74 (t, J=6.2 Hz, 2H), 4.67 (d, J=2.1 Hz, 1H), 3.14 (m, 1H) 1.99 (m, 4H) ppm; MS [M−OH] 547.4.

Workup

  1. customto quench
  2. customthe reaction
  3. additionThe mixture was poured into a seperatory funnel
  4. extractionextracted with dichloromethane (4×10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custom(3R,4S)-4-(2′-bromo-5′-hydroxybiphenyl-4-yl)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one was purified by chromatography (12 g silica gel, 5% to 95% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-d4f9b27ef7ed400db8bf2aad57add15d
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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