Potassium Carbonate → HCID 86600751, compound

HRID 2252456Notes

Reaction equation

HRID 2252456 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](B4OC(C)(C)C(C)(C)O4)=[CH:14][CH:13]=3)[C@@H:10]([CH2:27][CH2:28][C@@H:29]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[OH:30])[C:9]2=[O:38])=[CH:4][CH:3]=1.[CH2:39]([O:46][C@@H:47]1[C@@H:54]([O:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[C@H:53]([O:63][CH2:64][C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[C@@H:52]([CH2:71][O:72][C:73]2[CH:78]=[CH:77][CH:76]=[C:75](Br)[CH:74]=2)[O:51][CH:48]1[O:49][CH3:50])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C(CCO)=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:39]([O:46][C@@H:47]1[C@@H:54]([O:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[C@H:53]([O:63][CH2:64][C:65]2[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=2)[C@@H:52]([CH2:71][O:72][C:73]2[CH:74]=[C:75]([C:15]3[CH:14]=[CH:13][C:12]([C@@H:11]4[C@@H:10]([CH2:27][CH2:28][C@@H:29]([C:31]5[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=5)[OH:30])[C:9](=[O:38])[N:8]4[C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)=[CH:17][CH:16]=3)[CH:76]=[CH:77][CH:78]=2)[O:51][C@@H:48]1[O:49][CH3:50])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 69125242HCID 69125242, compoundHCID 69125699HCID 69125699, compound

Product 1

HCID 86600751HCID 86600751, compoundYield 85%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 882672-Methylphenethyl alcoholSolvent

Conditions

Temperature
85 °C

Procedure

(3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]azetidin-2-one (64.1 mg, 0.12 mmol), methyl 2,3,4-tri-O-benzyl-6-O-(3-bromophenyl)-D-glucopyranoside (54.6 mg, 0.09 mmol), and potassium carbonate (88 μL, 2 M aqueous solution) were dissolved in 1:1 toluen-ethanol (1 mL total volume). The solution was degassed by evacuating the vessel and flushing with argon three times. Tetrakis(triphenylphosphine)palladium (5.1 mg, 0.004 mmol) was added and the solution degassed twice. The reaction was heated at 85° C. for 1 h. LCMS and TLC (1:1 hexane-ethyl acetate) analysis indicated consumption of the starting glycoside. The reaction was diluted into ethyl acetate (30 mL) and washed with water (2×10 mL). The combined aqueous washes were back extracted with ethyl acetate (2×10 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, concentrated in vacuo and purified by chromatography (12 g silica gel, 20% to 50% ethyl acetate-hexane) to afford methyl 2,3,4-tri-O-benzyl-6-O-(4′-{(2S,3R)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl}biphenyl-3-yl)-α-D-glucopyranoside (70.0 mg, 85% yield). 1H NMR (300 MHz, CDCl3) δ 7.55 (d, J=8.1 Hz, 2H), 7.39-6.84 (m, 29H), 5.01 (d, J=10.8 Hz, 1H), 4.89-4.80 (m, 3H), 4.73-4.64 (m, 4H), 4.52 (d, J=11.1 Hz, 1H), 4.15-4.12 (m, 2H), 4.08-4.-1 (m, 1H), 3.94-3.90 (m, 1H), 3.77-3.71 (m, 1H), 3.62 (dd, J=3.6 Hz, J=9.6 Hz, 1H), 3.39 (s, 3H), 3.13-3.10 (m, 1H), 2.03-1.89 (m, 4H) ppm.

Workup

  1. customThe solution was degassed
  2. customby evacuating the vessel
  3. customflushing with argon three times
  4. customthe solution degassed twice
  5. customconsumption of the starting glycoside
  6. additionThe reaction was diluted into ethyl acetate (30 mL)
  7. washwashed with water (2×10 mL)
  8. extractionThe combined aqueous washes were back extracted with ethyl acetate (2×10 mL)
  9. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. custompurified by chromatography (12 g silica gel, 20% to 50% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-c3ac0c6435614a9ab82bd00468a62db8
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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