Hydrochloric Acid → (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-carboxylic acid

HRID 1055557Notes

Reaction equation

HRID 1055557 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([CH2:53][OH:54])[CH2:11][O:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-:56].[Na+].[Br-].[K+].Cl[O-].[Na+].Cl>ClCCl>[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([C:53]([OH:56])=[O:54])[CH2:11][O:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 253877Potassium BromideHCID 516892Sodium BicarbonateHCID 23665760Sodium HypochloriteHCID 86685153[(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]methanol

Product 1

HCID 118377789(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-carboxylic acidYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °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]octan-1-yl]methanol 171 (1.1 g, 1.45 mmol, obtained from the synthetic method described in step 11 of example 17) in dichloromethane (20 mL) were added sodium bicarbonate (1.58 g, 18.85 mmol), potassium bromide (172.0 mg, 1.45 mmol) and 2,2,6,6-tetramethylpiperidinooxy (22.0 mg, 0.14 mmol) in turn at 0° C., and then sodium hypochlorite (10 mL, 11.80 mmol, 3.5% available chlorine) was added dropwise. The mixture was stirred at 0° C. for 30 min and then room temperature for 1.5 hours. The reaction mixture was acidified with aqueous HCl until pH becomes 4 and partitioned. The aqueous layer was extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with saturated aqueous sodium chloride (50 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to give the title compound 18a (0.74 g, 66.0%) as pale yellow oil. This material was not further purified.

Workup

  1. waitroom temperature for 1.5 hours
  2. custompartitioned
  3. extractionThe aqueous layer was extracted with ethyl acetate (30 mL×3)
  4. washThe combined organic layers were washed with saturated aqueous sodium chloride (50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-9b523399e74047e98e2511a3b613d899
Source dataset
uspto-grants-2016_07
Patent number
US09394329B2

Reaction notes

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