Diethyl chlorophosphate → HCID 70907155, compound

HRID 1914507Notes

Reaction equation

HRID 1914507 reaction equation
[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][C:12]3[CH:13]=[C:14]([C@H:20]4[C@H:25]([OH:26])[C@@H:24]([OH:27])[C@H:23]([OH:28])[C@@H:22]([CH2:29][OH:30])[O:21]4)[CH:15]=[CH:16][C:17]=3[CH2:18][CH3:19])=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.[CH2:31]([O:33][P:34](Cl)([O:36][CH2:37][CH3:38])=[O:35])[CH3:32]>N1C=CC=CC=1>[CH2:31]([O:33][P:34](=[O:35])([O:36][CH2:37][CH3:38])[O:30][CH2:29][C@@H:22]1[C@@H:23]([OH:28])[C@H:24]([OH:27])[C@@H:25]([OH:26])[C@H:20]([C:14]2[CH:15]=[CH:16][C:17]([CH2:18][CH3:19])=[C:12]([CH2:11][C:9]3[CH:8]=[CH:7][C:6]4[O:1][CH2:2][CH2:3][O:4][C:5]=4[CH:10]=3)[CH:13]=2)[O:21]1)[CH3:32]

Participants

4

Reactant 2

HCID 13139Diethyl chlorophosphateHCID 52913524Licogliflozin2×

Product 1

HCID 70907155HCID 70907155, compoundYield 33.2%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a stirred solution of (2S,3R,4R,5S,6R)-2-[3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-4-ethyl-phenyl]-6-hydroxymethyl-tetrahydro-pyran-3,4,5-triol (Intermediate 2, 500 mg, 1.2 mmol) in pyridine (5 ml) was added diethylchlorophosphate (0.27 ml, 1.9 mmol) at −40° C. After stirring for 1 h at same temperature, reaction was quenched with the addition of 1N HCl and extracted with ethyl acetate (2×10 ml). Combined organic layers were washed with brine (10 ml), dried over sodium sulfate, concentrated and purified by preparative HPLC to give 220 mg of phosphoric acid (2R,3S,4R,5R,6S)-6-[3-(2,3-dihydro-benzo[1,4]dioxin-6-ylmethyl)-4-ethyl-phenyl]-3,4,5-trihydroxy-tetrahydro-pyran-2-ylmethyl ester diethyl ester as a white solid.

Workup

  1. customwas quenched with the addition of 1N HCl
  2. extractionextracted with ethyl acetate (2×10 ml)
  3. washCombined organic layers were washed with brine (10 ml)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-fe95fa0ee91b4e80845c2ace49f9f24e
Source dataset
uspto-grants-2013_12
Patent number
US08614195B2

Reaction notes

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