Sodium Hydroxide → HCID 16039141, compound

HRID 2252443Notes

Reaction equation

HRID 2252443 reaction equation
[Si]([O:8][C:9]1[CH:10]=[C:11]([C:15]2[CH:20]=[CH:19][C:18]([C@H:21]3[N:24]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:23](=[O:31])[C@@H:22]3[CH2:32][CH2:33][C@H:34]([O:42][Si](C(C)(C)C)(C)C)[C:35]3[CH:40]=[CH:39][C:38]([F:41])=[CH:37][CH:36]=3)=[CH:17][CH:16]=2)[CH:12]=[CH:13][CH:14]=1)(C(C)(C)C)(C)C.F.[OH-].[Na+].P([O-])([O-])([O-])=O.[Na+].[Na+].[Na+].C(=O)(O)[O-].[Na+]>C(#N)C>[F:41][C:38]1[CH:37]=[CH:36][C:35]([C@@H:34]([OH:42])[CH2:33][CH2:32][C@@H:22]2[C@@H:21]([C:18]3[CH:19]=[CH:20][C:15]([C:11]4[CH:12]=[CH:13][CH:14]=[C:9]([OH:8])[CH:10]=4)=[CH:16][CH:17]=3)[N:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:23]2=[O:31])=[CH:40][CH:39]=1

Participants

8

Reactant 6

HCID 14798Sodium HydroxideHCID 14917Hydrofluoric AcidHCID 24243Trisodium PhosphateHCID 516892Sodium BicarbonateHCID 69116717HCID 69116717, compoundHCID 178435178HCID 178435178, compound

Product 1

HCID 16039141HCID 16039141, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(3R,4S)-3-[(3S)-3-(4-Fluorophenyl)-3-hydroxypropyl]-4-(3′-hydroxybiphenyl-4-yl)-1-phenylazetidin-2-one was synthesized in a manner similar to that described in Example 42. (3R,4S)-4-(3′-{[tert-Butyl(dimethyl)silyl]oxy}biphenyl-4-yl)-3-[(3S)-3-{[tert-butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-1-phenylazetidin-2-one (0.60 g, 0.86 mmol) was stirred at room temperature in acetonitrile (18 mL) in a 40 ml polypropylene vial fitted with a screw cap. Hydrogen fluoride (48% aqueous, 2.0 mL, 48 mmol) was dripped in and stirring was continued at room temperature overnight. The reaction mixture was poured into an aqueous solution of 1 N sodium hydroxide (45 mL) buffered with 1 M sodium phosphate (45 mL, pH 7.4), then the pH of the solution was brought to pH 8 with the addition of aqueous 10% sodium bicarbonate solution. The mixture was extracted with ethyl acetate and the organic solution was washed successively with 10% sodium bicarbonate solution (2×), water (2×) and brine. The organic solution was dried over sodium sulfate, filtered and the solvent was removed by rotary evaporation under reduced pressure. Pure (3R,4S)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(3′-hydroxybiphenyl-4-yl)-1-phenylazetidin-2-one was obtained as a white foam (0.35 g, 87%) by chromatography over silica gel using ethyl acetate-hexane (gradient: 10% ethyl acetate to 60%) 1H NMR (300 MHz, CDCl3) δ 7.56 (d, J=8.2, Hz, 2H), 7.39 (d, J=8.2 Hz, 2H), 7.0-7.3 (m, 12H), 6.80-6.86 (m, 1H), 5.00 (br s, 1H), 4.74 (t, J=6.2 Hz, 1H), 4.69 (d, J=2.2 Hz, 1H), 3.1-3.2 (m, 1H), 2.20 (br s, 1H), 1.8-2.1 (m, 4H) ppm; MS [M+HCO2−]− 512.

Workup

  1. custom(3R,4S)-3-[(3S)-3-(4-Fluorophenyl)-3-hydroxypropyl]-4-(3′-hydroxybiphenyl-4-yl)-1-phenylazetidin-2-one was synthesized in a manner similar to
  2. customfitted with a screw
  3. customcap
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe organic solution was washed successively with 10% sodium bicarbonate solution (2×), water (2×) and brine
  6. dry with materialThe organic solution was dried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was removed by rotary evaporation under reduced pressure

Sources & evidence

ORD record
ord-c4217049ebcf4bfbb2cfcbbc0bc2aee3
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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