Formic Acid → HCID 69084238, compound

HRID 1396281Notes

Reaction equation

HRID 1396281 reaction equation
C([O:4][C@@H:5]1[C@@H:13]([C@@:14]([OH:20])([CH3:19])[C:15]([F:18])([F:17])[F:16])[O:12][C@H:11]2[C@H:7]([N:8]=[C:9]([N:21](C)[C:22](=O)OC(C)(C)C)[S:10]2)[C@H:6]1[O:30]CC=C)C=C.CCN(CC)CC.C(O)=O>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:22][NH:21][C:9]1[S:10][C@H:11]2[O:12][C@H:13]([C@@:14]([OH:20])([CH3:19])[C:15]([F:16])([F:17])[F:18])[C@@H:5]([OH:4])[C@H:6]([OH:30])[C@H:7]2[N:8]=1

Participants

6

Reactant 3

HCID 284Formic Acid2×HCID 8471TriethylamineHCID 86701119HCID 86701119, compound

Product 1

HCID 69084238HCID 69084238, compoundYield 25.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 119 (4.5 g, 9 mmol) in 1,4-dioxane (50 mL) was added Pd(PPh3)4 (2.1 g, 1.8 mmol), Et3N (23 g, 22.7 mmol) and HCOOH (0.8 g, 18 mmol) at 25° C. under N2 atmosphere. After 20 min at 60° C., additional HCOOH (6.3 g, 136 mmol) was added and the mixture was stirred for additional 12 hours at 60° C., then quenched by H2O (60 mL), extracted with dichloromethane (2×40 mL) to remove the organic impurities. The pH value of aqueous phase was adjusted to 7-8 by saturated aqueous NaHCO3, then concentrated under reduced pressure to give a residue, which was purified by a silica gel column, eluted with 2%-10% methanol in dichloromethane to give the mixture of the two epimer. Further separation by Prep HPLC [(Agilent 1200 prep HPLC): Column, Sun Fire Prep C18*50 mm 5 um; mobile phase, WATER with CH3CN (5% CH3CN up to 40% in 10 min); Detector, UV, 220 nm] to afford (3aR,5S,6S,7R,7aR)-2-(methylamino)-5-((S)-1,1,1-trifluoro-2-hydroxypropan-2-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as white solid (730 mg, 25.4%), Faster eluting isomer. (ES, m/z): 317.0; 1HNMR (300 MHz, D2O) δ 6.27 (d, J=6.9 Hz, 1H), 4.38-4.41 (m, 1H), 4.22-4.23 (m, 1H), 3.94-3.97 (d, J=8.4 Hz, 1H), 3.56-3.60 (d, J=8.4 Hz, 1H), 2.77 (s, 3H), 1.34 (s, 31-1); and (3aR,5S,6S,7R,7aR)-2-(methylamino)-5-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol as white solid (810 mg, 28.2%), Slower eluting isomer. (ES, m/z): 317.0; 1HNMR (300 MHz, D2O) δ 6.26 (d, J=6.9 Hz, 1H), 4.37-4.39 (m, 1H), 4.18-4.20 (m, 1H), 3.96-3.99 (m, 1H), 3.60-3.62 (d, J=8.4 Hz, 1H), 2.77 (s, 3H), 1.33 (s, 3H).

Workup

  1. customquenched by H2O (60 mL)
  2. extractionextracted with dichloromethane (2×40 mL)
  3. customto remove the organic impurities
  4. concentrationconcentrated under reduced pressure
  5. customto give a residue, which
  6. customwas purified by a silica gel column
  7. washeluted with 2%-10% methanol in dichloromethane
  8. customto give
  9. additionthe mixture of the two epimer
  10. customFurther separation by Prep HPLC [(Agilent 1200 prep HPLC)
  11. waitmobile phase, WATER with CH3CN (5% CH3CN up to 40% in 10 min)

Sources & evidence

ORD record
ord-00b38e6fba364fc88a8d3039d22a329a
Source dataset
uspto-grants-2014_12
Patent number
US08901087B2

Reaction notes

Loading…