Trifluoroacetic acid → HCID 71273704, compound

HRID 1501941Notes

Reaction equation

HRID 1501941 reaction equation
O[C:2]1([C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[C:25](=[O:29])[O:24][CH2:23][CH2:22]3)[O:7][CH2:6][C@@H:5]2[CH2:8][N:9](C(OC(C)(C)C)=O)[CH2:10][CH2:11][N:4]2[CH2:3]1.C(O)(C(F)(F)F)=O.[SiH](CC)(CC)CC>>[CH2:6]1[C@@H:5]2[CH2:8][NH:9][CH2:10][CH2:11][N:4]2[CH2:3][C@@H:2]([C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[C:25](=[O:29])[O:24][CH2:23][CH2:22]3)[O:7]1

Participants

4

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 12052TriethylsilaneHCID 86727027HCID 86727027, compound

Product 1

HCID 71273704HCID 71273704, compound

Conditions

Temperature
0 °C

Procedure

tert-Butyl(9aS)-3-hydroxy-3-(1-oxo-3,4-dihydro-1H-isochromen-6-yl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate (1.84 g, 4.55 mmol) was diluted with TFA (18 mL, 234 mmol) and cooled to 0° C. Some off gassing was apparent and after a few minutes a homogenous solution had been formed. Approximately 5 minutes post-TFA addition, Et3SiH (5.09 mL, 31.8 mmol) was added and the reaction mixture allowed to slowly warm to RT (allowed to warm naturally in the ice bath) where it was stirred for 18 h. The trans:cis diastereomeric ratio appeared to be ˜95:5. The reaction vessel was transferred to a rotary evaporator and concentrated in vacuo to a two phase liquid. This crude material was diluted with CH2Cl2 washed with NaHCO3, aq then water. The separately kept aqueous layers were subsequently extracted once with the same portion of CH2Cl2, the combined organics dried with MgSO4, filtered and concentrated in vacuo. The crude residue was dried under house vacuum then the mixture was further purified by flash chromatography (2% MeOH 2% Et3N in CH2Cl2) to afford the title compound.

Workup

  1. waitSome off gassing was apparent and after a few minutes
  2. customa homogenous solution had been formed
  3. additionwas added
  4. temperatureto slowly warm to RT (
  5. customThe reaction vessel was transferred to a rotary evaporator
  6. concentrationconcentrated in vacuo to a two phase liquid
  7. additionThis crude material was diluted with CH2Cl2
  8. washwashed with NaHCO3
  9. extractionThe separately kept aqueous layers were subsequently extracted once with the same portion of CH2Cl2
  10. dry with materialthe combined organics dried with MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. dry with materialThe crude residue was dried under house vacuum
  14. customthe mixture was further purified by flash chromatography (2% MeOH 2% Et3N in CH2Cl2)

Sources & evidence

ORD record
ord-63e019f9ecc4432bb0ce6c5134d9c048
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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