Hydrofluoric Acid → HCID 11488566, compound

HRID 2252433Notes

Reaction equation

HRID 2252433 reaction equation
[Si]([O:8][C@H:9]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=1)[CH2:10][CH2:11][C@@H:12]1[C@@H:15]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=3)=[CH:18][C:17]=2[OH:29])[N:14]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:13]1=[O:36])(C(C)(C)C)(C)C.F>C(#N)C>[OH:29][C:17]1[CH:18]=[C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([OH:28])[CH:23]=2)[CH:20]=[CH:21][C:16]=1[C@H:15]1[N:14]([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:13](=[O:36])[C@@H:12]1[CH2:11][CH2:10][C@@H:9]([C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=1)[OH:8]

Participants

5

Reactant 3

HCID 14917Hydrofluoric AcidHCID 69116789HCID 69116789, compoundHCID 178435178HCID 178435178, compound

Product 1

HCID 11488566HCID 11488566, compoundYield 89.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

(3R,4S)-3-[(3S)-3-{[tert-Butyl(dimethyl)silyl]oxy}-3-(4-fluorophenyl)propyl]-4-(3,3′-dihydroxybiphenyl-4-yl)-1-phenylazetidin-2-one (73 mg, 0.122 mmol) was dissolved in acetonitrile (5 mL) and transferred to a polypropylene conical vial. 48% Hydrofluoric acid (1 mL) was added dropwise and the reaction stirred at room temperature for 1 h. The reaction was quenched with 1 N sodium hydroxide (24 mL) and transferred to a flask containing pH 7.4 phosphate buffer (24 mL). The pH of the solution was adjusted to 7.5-8.0 with saturated sodium bicarbonate solution then extracted with ethyl acetate (3×). The combined organic layers were washed with saturated sodium bicarbonate solution (2×), water, brine, dried over sodium sulfate, filtered, concentrated and purified by chromatography (12 g silica gel, 40% to 100% ethyl acetate-hexane) to afford (3R,4S)-4-(3,3′-dihydroxybiphenyl-4-yl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-1-phenylazetidin-2-one (53 mg, 69% yield)); 1H NMR (300 MHz, CDCl3) δ 7.30-7.13 (m, 7H), 7.08-6.85 (m, 8H), 6.78 (ddd, J=8.1, 2.3, 0.9 Hz, 1H), 5.04 (d, J=2.3 Hz, 1H), 4.61 (t, J=5.9 Hz, 1H), 3.07 (ddd, J=5.7, 1.8, 1.5 Hz, 1H), 2.08-1.80 (m, 4H) ppm; MS [M+H]+ 584.0 [M−H]− 582.0.

Workup

  1. customThe reaction was quenched with 1 N sodium hydroxide (24 mL)
  2. customtransferred to a flask
  3. additioncontaining pH 7.4 phosphate buffer (24 mL)
  4. extractionthen extracted with ethyl acetate (3×)
  5. washThe combined organic layers were washed with saturated sodium bicarbonate solution (2×), water, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by chromatography (12 g silica gel, 40% to 100% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-308f97af28c74733894c27e018b34328
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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