Water → HCID 131736392, compound

HRID 1055594Notes

Reaction equation

HRID 1055594 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])=[C:43]([F:50])[C:42]=4[F:51])[CH:34]=3)[O:32][C@@:10]1([C:52]([OH:54])=[O:53])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[C:60](=O)(O)[O-].[Na+].O>CO>[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:27]=[CH:28][CH:29]=[CH:30][CH:31]=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])=[C:43]([F:50])[C:42]=4[F:51])[CH:34]=3)[O:32][C@@:10]1([C:52]([O:54][CH3:60])=[O:53])[CH2:11][O:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 1118Sulfuric AcidHCID 516892Sodium BicarbonateHCID 118377859HCID 118377859, compound

Product 1

HCID 131736392HCID 131736392, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxy-2,3-difluoro-phenyl) methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-carboxylic acid 24a (507 mg, 0.67 mmol) in methanol (10 mL) was added concentrated sulphuric acid (0.04 mL, 0.74 mmol) at room temperature. The mixture was warmed up to 40° C. and stirred for 7 hours. The reaction mixture was cooled to room temperature and adjusted with saturated aqueous sodium bicarbonate to pH 7. To the mixture was added 10 mL of water and the resulting mixture was extracted with ethyl acetate (15 mL×3). The combined organic layers were 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 24b as colorless oil (320 mg, 62%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ(ppm): 7.39 (m, 10H), 7.20 (m, 6H), 6.89 (d, 2H), 6.63 (t, 1H), 6.51 (t, 1H), 4.83 (m, 3H), 4.63 (d, 1H), 4.53 (d, 1H), 4.30 (d, 1H), 4.20 (d, 2H), 4.08-3.97 (m, 5H), 3.90 (d, 1H), 3.75 (m, 1H), 3.71 (s, 3H), 1.44 (t, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe resulting mixture was extracted with ethyl acetate (15 mL×3)
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by silica gel chromatography
  7. washeluted with PE/EtOAc(v/v)=15/1

Sources & evidence

ORD record
ord-003032b58657453f9289247fd5eeaf4b
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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