(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoro ethoxy)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-(2,2,2-trifluoroethoxyl)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol

HRID 1055555Notes

Reaction equation

HRID 1055555 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][C:49]([F:52])([F:51])[F:50])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:53]=[O:54])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:55][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][CH2:48][C:49]([F:52])([F:51])[F:50])=[CH:45][CH:46]=4)[CH:34]=3)[O:32][C@@:10]1([CH:53]([OH:54])[CH3:55])[CH2:11][O:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 118377846(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoro ethoxy)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carbaldehydeHCID 178418573HCID 178418573, compound

Product 1

HCID 1183777981-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoroethoxyl)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanolYield 69.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-10 °C

Procedure

To a solution of (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoroethoxyl)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carbaldehyde 17m (1.85 g, 2.43 mmol) in dry tetrahydrofuran (40 mL) was added dropwise methylmagnesium bromide (1.22 mL, 3.66 mmol, 3M in ethyl ether) under N2 at −10° C. The mixture was stirred at −10° C. for 15 min and then room temperature for 3 hours. The reaction mixture was quenched with saturated aqueous ammonium chloride (40 mL) and extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (15 mL×3), 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 17n as pale yellow oil (1.3 g, 69.1%). The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, CDCl3) δ(ppm): 7.41 (d, 1H), 7.36 (m, 4H), 7.30 (m, 5H), 7.24 (m, 3H), 7.20 (d, 1H), 7.16 (t, 2H), 7.09 (d, 2H), 6.89 (d, 2H), 6.76 (d, 2H), 4.97 (m, 1H), 4.90 (d, 1H), 4.81-4.73 (m, 2H), 4.37 (d, 1H), 4.29-4.20 (m, 3H), 4.08-3.98 (m, 3H), 3.96 (d, 1H), 3.89 (d, 1H), 3.79 (m, 1H), 3.72 (t, 1H), 3.66 (m, 1H), 1.25 (d, 3H).

Workup

  1. waitroom temperature for 3 hours
  2. customThe reaction mixture was quenched with saturated aqueous ammonium chloride (40 mL)
  3. extractionextracted with ethyl acetate (50 mL×3)
  4. washThe combined organic layers were washed with saturated aqueous sodium chloride (15 mL×3)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by silica gel chromatography
  9. washeluted with PE/EtOAc(v/v)=15/1

Sources & evidence

ORD record
ord-8cb28237034f46a2bf4fefbc3da670d5
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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