Hydrochloric Acid → HCID 67305029, compound

HRID 1009138Notes

Reaction equation

HRID 1009138 reaction equation
[CH2:1]([N:4]([C:8]([CH3:11])([CH3:10])C)C(=O)[O-])[CH:2]=[CH2:3].O[CH:13]([C:18]1[CH:19]=C2[C@@H](N)C[C:25]3([CH2:31][CH2:30][CH2:29]3)[O:24][C:21]2=[N:22][CH:23]=1)[C:14]([CH3:17])([CH3:16])[CH3:15].CCN(S(F)(F)[F:38])CC.Cl.O1CCOCC1>CO.C(Cl)Cl.C1(C)C=CC=CC=1>[CH2:1]([NH:4][C@@H:8]1[C:10]2[C:21](=[N:22][CH:23]=[C:18]([CH:13]([F:38])[C:14]([CH3:17])([CH3:16])[CH3:15])[CH:19]=2)[O:24][C:25]2([CH2:31][CH2:30][CH2:29]2)[CH2:11]1)[CH:2]=[CH2:3]

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 312751,4-DioxaneHCID 123472(Diethylamino)sulfur trifluorideHCID 86614127HCID 86614127, compound

Product 1

HCID 67305029HCID 67305029, compoundYield 103%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

To a 250 mL RBF was added N-allyl-N-t-butylcarbamate-(4′S)-6′-(1-hydroxy-2,2-dimethylpropyl)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-b]pyridin]-4′-amine (4.01 g, 9.6 mmol), toluene (100 mL), a dry ice bath, and after cooling for 20 minutes DAST (1.81 ml, 14 mmol) was added. After 1 hour, LC-MS shows Reactant 1 consumed. The reaction was quenched with sat'd NH4Cl (20 mL). The layers were separated and the aqueous layer extracted with EtOAc (20 mL). The combined organic layers were concentrated in vacuo to give a golden oil. The oil was taken up in MeOH (50 mL) and treated with HCl, 4M in dioxane (5.0 ml, 20 mmol). After 1.5 hours, no changes were seen by LC-MS. The reaction was treated with an additional HCl (5 mL) and heated to 60° C. After stirring for 5 hours, the solution was allowed to cool to RT. After a further 16 hours, the reaction was concentrated in vacuo to give a brown oil, which was taken up in DCM and washed with sat'd NaHCO3, brine and concentrated in vacuo to give N-allyl-(4′S)-6′-(1-fluoro-2,2-dimethylpropyl)-3′,4′-dihydrospiro[cyclobutane-1,2′-pyrano[2,3-b]pyridin]-4′-amine (3.15 g) as a brown oil. MS m/z: 319 (M+1). The crude material was used without further purification in the next step.

Workup

  1. additionwas added
  2. customconsumed
  3. customThe reaction was quenched with sat'd NH4Cl (20 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer extracted with EtOAc (20 mL)
  6. concentrationThe combined organic layers were concentrated in vacuo
  7. customto give a golden oil
  8. waitAfter 1.5 hours
  9. temperatureto cool to RT
  10. waitAfter a further 16 hours
  11. concentrationthe reaction was concentrated in vacuo
  12. customto give a brown oil, which
  13. washwashed with sat'd NaHCO3, brine
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-216977b320d642139d5c296e2b3803ef
Source dataset
uspto-grants-2011_07
Patent number
US07973047B2

Reaction notes

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