Acetic Acid → HCID 67280601, compound

HRID 1516332Notes

Reaction equation

HRID 1516332 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([C:6]([NH:8][C@H:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([N:18]4[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]4)[CH:16]=3)[CH2:11][C@@H:10]2[OH:31])=[O:7])=[CH:4][CH:3]=1.Cl.[O:35]1[CH2:38][C:37](=O)[CH2:36]1.C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)(O)[O-].[Na+]>O1CCOCC1>[F:1][C:2]1[CH:33]=[CH:32][C:5]([C:6]([NH:8][C@H:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([N:18]4[CH2:23][CH2:22][N:21]([CH:37]5[CH2:38][O:35][CH2:36]5)[CH2:20][CH2:19]4)[CH:16]=3)[CH2:11][C@@H:10]2[OH:31])=[O:7])=[CH:4][CH:3]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 67280318HCID 67280318, compound

Product 1

HCID 67280601HCID 67280601, compoundYield 81.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of tert-butyl 4-[(2S,3S)-3-[(4-fluorobenzoyl)amino]-2-hydroxy-indan-5-yl]piperazine-1-carboxylate (300 mg, 0.659 mmol) in 1,4-dioxane (5.0 mL), add 4 M hydrogen chloride in dioxane (5.0 mL) at room temperature and stir for 1 hr. Concentrate the suspension in vacuo. Add to the residue saturated aqueous sodium bicarbonate (50 mL) and extract with ethyl acetate (3×50 mL). Wash the combined organic layers with brine, dry over sodium sulfate, and concentrate in vacuo. Dissolve the residue in methanol (20 mL) and add 3-oxetanone (142 mg, 1.98 mmol), glacial acetic acid (170 μL, 2.96 mmol), and crushed activated 4 Å molecular sieves. Stir the resulting suspension at 50° C. for 1 hr. Add sodium cyanoborohydride (131 mg, 1.98 mmol) at room temperature and stir overnight. Add a saturated sodium bicarbonate solution (20 mL) and stir for 20 min. Extract with dichloromethane (3×50 mL) and wash the combined organic layers with water and brine. Dry the organic portion over sodium sulfate, filter, and concentrate to obtain the title compound (220 mg, 81%). LC-ES/MS m/z 412 [M+H]+.

Workup

  1. concentrationConcentrate the suspension in vacuo
  2. additionAdd to the residue saturated aqueous sodium bicarbonate (50 mL)
  3. extractionextract with ethyl acetate (3×50 mL)
  4. washWash the combined organic layers with brine
  5. dry with materialdry over sodium sulfate
  6. concentrationconcentrate in vacuo
  7. dissolutionDissolve the residue in methanol (20 mL)
  8. customcrushed activated 4 Å molecular sieves
  9. stirringStir the resulting suspension at 50° C. for 1 hr
  10. stirringstir for 20 min
  11. extractionExtract with dichloromethane (3×50 mL)
  12. washwash the combined organic layers with water and brine
  13. dry with materialDry the organic portion over sodium sulfate
  14. filtrationfilter
  15. concentrationconcentrate

Sources & evidence

ORD record
ord-41d9509edfe549aba5d479328ac39a9d
Source dataset
uspto-grants-2012_07
Patent number
US08227468B2

Reaction notes

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