(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carbaldehyde → 1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol

HRID 1055541Notes

Reaction equation

HRID 1055541 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][C:48]([F:51])([F:50])[F:49])=[CH:43][CH:42]=4)[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: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:42]=[CH:43][C:44]([O:47][C:48]([F:51])([F:50])[F:49])=[CH:45][CH:46]=4)[CH:34]=3)[O:32][C@@:10]1([CH:52]([OH:53])[CH3:54])[CH2:11][O:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 118377816(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carbaldehydeHCID 178418573HCID 178418573, compound

Product 1

HCID 1183778041-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanolYield 14.4%

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-(trifluoromethoxy) phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carbaldehyde 15p (0.71 g, 0.95 mmol) in dry tetrahydrofuran (15 mL) was added dropwise methylmagnesium bromide (0.64 mL, 1.91 mmol, 3M in tetrahydrofuran) under N2 at 0° C. After the addition, the mixture was warmed up to room temperature and stirred for 3 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride (3 mL). To the mixture was added 20 mL of saturated aqueous sodium chloride and the resulting mixture was partitioned. The aqueous layer was extracted with ethyl acetate (20 mL×2). The combined organic layers were washed with saturated aqueous sodium chloride (30 mL×2), 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)=15/1 to give the title compound 15q as colourless oil (104 mg, 14.3%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.45 (s, 1H), 7.40 (s, 2H), 7.38-7.29 (m, 9H), 7.25-7.14 (m, 6H), 7.06 (d, 2H), 6.92 (d, 2H), 4.97 (dd, 2H), 4.81 (d, 2H), 4.29 (d 2H), 4.13-4.07 (m, 3H), 4.06 (s, 3H), 3.84 (d 1H), 3.69 (d, 1H), 3.58 (s, 1H), 1.21 (d, 3H).

Workup

  1. additionAfter the addition
  2. customThe reaction mixture was quenched with saturated aqueous ammonium chloride (3 mL)
  3. additionTo the mixture was added 20 mL of saturated aqueous sodium chloride
  4. customthe resulting mixture was partitioned
  5. extractionThe aqueous layer was extracted with ethyl acetate (20 mL×2)
  6. washThe combined organic layers were washed with saturated aqueous sodium chloride (30 mL×2)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by silica gel chromatography
  11. washeluted with PE/EtOAc(v/v)=15/1

Sources & evidence

ORD record
ord-9f265aca00df415b896ad8d8cc2917f0
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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