HCID 118377862, compound → HCID 131736391, compound

HRID 1055591Notes

Reaction equation

HRID 1055591 reaction equation
[CH2:1]([O:8][C@H:9]1[C@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@:13]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[C:43]([F:50])[C:42]=4[F:51])[CH:34]=3)[O:32][C@@:10]1([CH:52]=[O:53])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:54][Mg]Br>O1CCCC1>[CH2:1]([O:8][C@H:9]1[C@H:15]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@:13]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[C:43]([F:50])[C:42]=4[F:51])[CH:34]=3)[O:32][C@@:10]1([CH:52]([OH:53])[CH3:54])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 118377862HCID 118377862, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 131736391HCID 131736391, compoundYield 36.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxy-2,3-difluoro-phenyl) methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carbaldehyde 23o (1.30 g, 1.75 mmol) in dry tetrahydrofuran (20 mL) was added dropwise methylmagnesium bromide (1.75 mL, 5.25 mmol, 3 M in ethyl ether) under N2 at 0° C. The mixture was stirred at room temperature for 4 hours. The reaction mixture was quenched with water (10 mL) and extracted with ethyl acetate (15 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (30 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=12/1 to give the title compound 23p as a white solid (0.48 g, 36%). The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, CDCl3) δ(ppm): 7.38 (m, 11H), 7.22 (m, 5H), 6.93 (m, 2H), 6.66 (s, 1H), 6.53 (m, 1H), 4.99 (m, 1H), 4.94 (d, 1H), 4.80 (m, 2H), 4.31 (m, 2H), 4.04 (m, 5H), 3.95 (m, 2H), 3.83 (m, 2H), 3.70 (m, 1H), 1.45 (t, 3H), 1.28 (d, 3H).

Workup

  1. customThe reaction mixture was quenched with water (10 mL)
  2. extractionextracted with ethyl acetate (15 mL×3)
  3. washThe combined organic layers were washed with saturated aqueous sodium chloride (30 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by silica gel chromatography
  8. washeluted with PE/EtOAc(v/v)=12/1

Sources & evidence

ORD record
ord-a5739b113be54ec3a7e453a28a4c0b23
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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