Trifluoroacetic acid → (4R,9aR)-6-(1-(R)-hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 1272154Notes

Reaction equation

HRID 1272154 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH:22]([OH:24])[CH3:23])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([C@H:22]([OH:24])[CH3:23])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67237860(4R,9aR)-6-(1-(RS)-Hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Product 1

HCID 67237861(4R,9aR)-6-(1-(R)-hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3.09 g (9.27 mmol) (4R,9aR)-6-(1-(RS)-hydroxy-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester in 33 mL dichloromethane was cooled to 0 deg C. and treated with 8.8 mL (12.7 g, 0.11 mol) trifluoroacetic acid. The cooling bath was removed and the volatile components were removed at a rotary evaporator. The remaining residue was purified by column chromatography on silica gel (0.032–0.063 mm) with dichloromethane:methanol:ammonia (19:1:0.1). The remaining oil was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution and extracted with dichloromethane until all product was removed from the aqueous phase. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The remaining light brown oil was purified by column chromatography on a Chiralpak-AD column with 7% ethanol/n-heptane yielding the desired compound as a light brown solid (36.5%).

Workup

  1. customThe cooling bath was removed
  2. customthe volatile components were removed at a rotary evaporator
  3. customThe remaining residue was purified by column chromatography on silica gel (0.032–0.063 mm) with dichloromethane:methanol:ammonia (19:1:0.1)
  4. customThe remaining oil was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution
  5. extractionextracted with dichloromethane until all product
  6. customwas removed from the aqueous phase
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated
  11. customThe remaining light brown oil was purified by column chromatography on a Chiralpak-AD column with 7% ethanol/n-heptane yielding the desired compound as a light brown solid (36.5%)

Sources & evidence

ORD record
ord-5921fd4536a1459e85bce59234070ded
Source dataset
uspto-grants-2007_04
Patent number
US07208494B2

Reaction notes

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