Sodium hydride → HCID 118377815, compound

HRID 1055528Notes

Reaction equation

HRID 1055528 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])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:50]([OH:52])[CH3:51])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:53](OCCl)(=[O:58])[C:54]([CH3:57])([CH3:56])[CH3:55].[H-].[Na+]>O1CCCC1>[CH3:55][C:54]([CH3:57])([CH3:56])[C:53]([O:52][CH:50]([C@:10]12[O:32][C@:13]([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][CH3:49])=[CH:45][CH:46]=4)[CH:34]=3)([O:12][CH2:11]1)[C@H:14]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@@H:15]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[C@@H:9]2[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[CH3:51])=[O:58]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 87885Chloromethyl pivalateHCID 118377829HCID 118377829, compound

Product 1

HCID 118377815HCID 118377815, compoundYield 27.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 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 1m (0.4 g, 0.56 mmol, obtained from the synthetic method described in step 11 of example 1) and chloromethyl pivalate (0.36 mL, 2.5 mmol) in tetrahydrofuran (20 mL) was added sodium hydride (77.8 mg, 1.95 mmol, 60% dispersion in Mineral oil) at 0° C. The mixture was heated to 40° C. and stirred for 48 hours. The resulting mixture was quenched with saturated ammonium chloride (20 mL), and then extracted with ethyl acetate (60 mL×3). The combined organic layers were washed with water (50 mL×2) and then saturated brine (50 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)=10/1 to give the title compound 14a as light yellow oil (125 mg, 27.8%). The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, CDCl3) δ (ppm): 7.42-7.30 (m, 10H), 7.28-7.15 (m, 6H), 7.07 (m, 2H), 6.91 (m, 2H), 6.76 (m, 2H), 5.20 (m, 1H), 4.98 (d, 1H), 4.89-4.82 (m, 2H), 4.31 (m, 1H), 4.25 (d, 1H), 4.11-3.80 (m, 7H), 3.86 (d, 1H), 3.70 (m, 2H), 1.41 (t, 3H), 1.27 (d, 3H), 1.20 (s, 9H).

Workup

  1. customThe resulting mixture was quenched with saturated ammonium chloride (20 mL)
  2. extractionextracted with ethyl acetate (60 mL×3)
  3. washThe combined organic layers were washed with water (50 mL×2)
  4. dry with materialsaturated brine (50 mL×3), 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-93abb78147ea4717999b53a039a2c164
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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