Acetic Anhydride → [(1R,3R,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-2-oxo-6,8-dioxabicyclo[3.2.1]octan-1-yl]methyl acetate

HRID 1055616Notes

Reaction equation

HRID 1055616 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@:14]2([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([CH2:32][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH2:40][CH3:41])=[CH:35][CH:34]=4)[CH:26]=3)[O:24][C@@:11]([CH2:42][OH:43])([CH2:12][O:13]2)[C:10]1=[O:44])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:45](OC(=O)C)(=[O:47])[CH3:46].C(N(CC)CC)C>ClCCl>[C:45]([O:43][CH2:42][C@:11]12[O:24][C@:14]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([CH2:32][C:33]4[CH:34]=[CH:35][C:36]([O:39][CH2:40][CH3:41])=[CH:37][CH:38]=4)[CH:26]=3)([O:13][CH2:12]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]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:10]2=[O:44])(=[O:47])[CH3:46]

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 118377830(1S,3R,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-2-one

Product 1

HCID 131736405[(1R,3R,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-2-oxo-6,8-dioxabicyclo[3.2.1]octan-1-yl]methyl acetateYield 84.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (1S,3R,4R,5S)-3,4-dibenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octan-2-one 28g (13.4 g, 21.8 mmol) in dichloromethane (40 mL) were added acetic anhydride (3.0 mL, 32.7 mmol) and triethylamine (6.0 mL, 43.6 mmol) at room temperature. The mixture was stirred at room temperature for 2 hours and quenched with water (100 mL). The resulting mixture was extracted with dichloromethane (100 mL×2). The combined organic phases were washed with saturated aqueous sodium chloride (100 mL×3), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=10/1 to give the title compound 28h as a pale yellow solid (12.1 g, 84.6%). The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, CDCl3) δ (ppm): 7.29 (m, 4H), 7.24 (m, 3H), 7.19 (s, 1H), 7.12 (d, 1H), 7.07 (m, 2H), 6.99 (d, 2H), 6.76 (m, 2H), 6.68 (d, 2H), 4.94 (d, 1H), 4.58 (d, 1H), 4.47 (d, 1H), 4.37 (d, 1H), 4.31 (m, 2H), 4.07 (d, 1H), 3.95 (m, 3H), 3.88 (m, 5H), 1.97 (s, 3H), 1.31 (t, 3H).

Workup

  1. customquenched with water (100 mL)
  2. extractionThe resulting mixture was extracted with dichloromethane (100 mL×2)
  3. washThe combined organic phases were washed with saturated aqueous sodium chloride (100 mL×3)
  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)=10/1

Sources & evidence

ORD record
ord-b98590f62fbc4467aa239b24ead02d15
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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