Ethanol, 2,2,2-trifluoro-, sodium salt (1:1) → (1S,3'R,4'S,5'S,6'R)-5-chloro-6-(4-ethylbenzyl)-6'-((2,2,2-trifluoroethoxy)methyl)-3',4',5',6'-tetrahydro-3H-spiro[isobenzofuran-1,2'-pyran]-3',4',5'-triol

HRID 1716962Notes

Reaction equation

HRID 1716962 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[O:18][C@@:17]3([C:26]4[C:21](=[CH:22][C:23]([Cl:36])=[C:24]([CH2:27][C:28]5[CH:33]=[CH:32][C:31]([CH2:34][CH3:35])=[CH:30][CH:29]=5)[CH:25]=4)[CH2:20][O:19]3)[C@H:16]([OH:37])[C@@H:15]([OH:38])[C@@H:14]2[OH:39])(=O)=O)=CC=1.[F:40][C:41]([F:45])([F:44])[CH2:42][O-:43].[Na+]>>[Cl:36][C:23]1[CH:22]=[C:21]2[C:26](=[CH:25][C:24]=1[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][CH3:35])=[CH:30][CH:29]=1)[C@:17]1([C@H:16]([OH:37])[C@@H:15]([OH:38])[C@H:14]([OH:39])[C@@H:13]([CH2:12][O:43][CH2:42][C:41]([F:45])([F:44])[F:40])[O:18]1)[O:19][CH2:20]2

Participants

3

Reactant 2

HCID 23677971Ethanol, 2,2,2-trifluoro-, sodium salt (1:1)HCID 59013460((1S,3'R,4'S,5'S,6'R)-5-chloro-6-(4-ethylbenzyl)-3',4',5'-trihydroxy-3',4',5',6'-tetrahydro-3H-spiro[isobenzofuran-1,2'-pyran]-6'-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 59013441(1S,3'R,4'S,5'S,6'R)-5-chloro-6-(4-ethylbenzyl)-6'-((2,2,2-trifluoroethoxy)methyl)-3',4',5',6'-tetrahydro-3H-spiro[isobenzofuran-1,2'-pyran]-3',4',5'-triol

Procedure

To ((1S,3′R,4′S,5′S,6′R)-5-chloro-6-(4-ethylbenzyl)-3′,4′,5′-trihydroxy-3′,4′,5′,6′-tetrahydro-3H-spiro[isobenzofuran-1,2′-pyran]-6′-yl)methyl 4-methylbenzenesulfonate (14 mg, 0.024 mmol) was added 1 mL of freshly prepared sodium trifluoroethoxide solution (1.5 M). After refluxing for 5 h at temperature, the reaction was quenched with 2 mL of water. The organic solvent was distilled off and the water layer was extracted with ethyl acetate. The combined organic layers were washed with brine prior to drying over Na2SO4. Concentration under reduced pressure provided the crude product, which was purified by preparative TLC to give 6 mg of title compound. 1H NMR (CD3OD, 300 MHz) δ 7.36 (s, 1H), 7.19 (s, 1H), 7.09 (s, 4H), 5.12 (d, J=13.2 Hz, 1H), 5.07 (d, J=13.2 Hz, 1H), 4.11 (d, J=15.5 Hz, 1H), 4.05 (d, J=15.5 Hz, 1H), 3.89-3.66 (m, 7H), 3.48 (t, J=9.2 Hz, 1H), 2.59 (q, J=7.8 Hz, 2H), 1.19 (t, J=7.8 Hz, 3H); MS ESI (m/z) 503 (M+1)+, calc. 502.

Workup

  1. temperatureAfter refluxing for 5 h at temperature
  2. customthe reaction was quenched with 2 mL of water
  3. distillationThe organic solvent was distilled off
  4. extractionthe water layer was extracted with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialto drying over Na2SO4
  7. concentrationConcentration under reduced pressure
  8. customprovided the crude product, which
  9. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-c990f623f2b442ff9a374682b9520884
Source dataset
uspto-grants-2010_09
Patent number
US07803778B2

Reaction notes

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