Tetrahydrofuran → HCID 118377820, compound

HRID 1055608Notes

Reaction equation

HRID 1055608 reaction equation
[NH2:1][CH2:2][CH:3]([C@:5]12[O:12][C@:9]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([CH2:20][C:21]4[CH:26]=[CH:25][C:24]([O:27][CH2:28][CH3:29])=[CH:23][CH:22]=4)[CH:14]=3)([O:10][CH2:11]1)[C@H:8]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C@@H:7]([O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[C@@H:6]2[O:46][CH2:47][C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[OH:4].[O:54]1CCC[CH2:55]1>>[CH2:47]([O:46][C@H:6]1[C@H:7]([O:38][CH2:39][C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=2)[C@@H:8]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C@:9]2([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([CH2:20][C:21]4[CH:22]=[CH:23][C:24]([O:27][CH2:28][CH3:29])=[CH:25][CH:26]=4)[CH:14]=3)[O:12][C@@:5]1([CH:3]1[O:4][C:55](=[O:54])[NH:1][CH2:2]1)[CH2:11][O:10]2)[C:48]1[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=1

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 118377849HCID 118377849, compound

Product 1

HCID 118377820HCID 118377820, compoundYield 69.5%

Procedure

To a solution of 2-amino-1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl) methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethanol 10b (50 mg, 0.07 mmol, obtained from the synthetic method described in step 2 of example 10) in tetrahydrofuran (10 mL) was added N,N′-carbonyldiimidazole (14.3 mg, 0.09 mmol) at room temperature. The mixture was stirred at room temperature for 4 hours. The reaction mixture was quenched with water (5 mL) and extracted with ethyl acetate (20 mL×2). The combined organic layers were washed with water (10 mL×2) and then saturated aqueous sodium chloride (10 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)=10/1 to give the title compound 27a as a white solid (36 mg, 69.5%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.42 (m, 1H), 7.34 (m, 12H), 7.20 (m, 3H), 7.10 (m, 2H), 6.91 (m, 2H), 6.78 (m, 2H), 5.46 (s, 1H), 4.95 (t, 2H), 4.84 (t, 2H), 4.30 (dd, 2H), 4.22 (d, 1H), 4.11 (m, 1H), 4.02 (m, 5H), 3.85 (d, 1H), 3.70 (d, 1H), 3.54 (m, 2H), 3.36 (d, 1H), 1.45 (t, 3H).

Workup

  1. customThe reaction mixture was quenched with water (5 mL)
  2. extractionextracted with ethyl acetate (20 mL×2)
  3. washThe combined organic layers were washed with water (10 mL×2)
  4. dry with materialsaturated aqueous sodium chloride (10 mL×2), dried 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)=10/1

Sources & evidence

ORD record
ord-213367a4530945ac8c6fa487d659af1c
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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