Trifluoroacetic acid → 6-pyrimidin-2-yl-6-azaspiro[3,3]heptane TFA salt

HRID 929165Notes

Reaction equation

HRID 929165 reaction equation
[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[N:8]1[CH:13]=[CH:12][CH:11]=[N:10][C:9]=1[N:14]1[CH2:17][C:16]2([CH2:20]N(C(OC(C)(C)C)=O)[CH2:18]2)[CH2:15]1>>[OH:5][C:3]([C:2]([F:7])([F:6])[F:1])=[O:4].[N:10]1[CH:11]=[CH:12][CH:13]=[N:8][C:9]=1[N:14]1[CH2:15][C:16]2([CH2:18][CH2:2][CH2:20]2)[CH2:17]1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 90041826HCID 90041826, compound

Product 1

HCID 1317350896-pyrimidin-2-yl-6-azaspiro[3,3]heptane TFA salt

Conditions

Temperature
2.5 °C

Procedure

A 1 L round-bottom flask was charged with trifluoroacetic acid (153.0 mL) and the mixture cooled to 0-5° C. Tert-butyl 2-pyrimidin-2-yl-2,6-diazaspiro[3,3]heptane-6-carboxylate (51.0 g, 0.19 mol) was added and the reaction mixture was stirred at 0-5° C. until dissolution occurred. Then the reaction mixture warmed to 20-25° C. and stirred for 60 min. The reaction mixture was concentrated, azeotroped with DCM (2×50.0 mL), and diluted with DCM (150.0 mL). This solution was slowly added to a well-stirred solution of MTBE (600.0 mL). The resultant slurry was heated to 35-40° C. to give a free-flowing off-white solid. The slurry was cooled to <15° C. and filtered to afford the title compound. 1H NMR (300 MHz, CD3OD) δ: 8.39 (d, J=5.03 Hz, 2H), 6.77 (t, J=5.03 Hz, 1H), 4.35 (s, 4H), 4.32 (s, 4H); 13C NMR (75 MHz, DMSO-d6) δ: 162.5, 158.2, 111.2, 60.0, 55.3, 36.0; LC/MS: m/z=177 [M]+.

Workup

  1. temperatureThen the reaction mixture warmed to 20-25° C.
  2. stirringstirred for 60 min
  3. concentrationThe reaction mixture was concentrated
  4. customazeotroped with DCM (2×50.0 mL)
  5. additiondiluted with DCM (150.0 mL)
  6. additionThis solution was slowly added to a well-stirred solution of MTBE (600.0 mL)
  7. temperatureThe resultant slurry was heated to 35-40° C.
  8. customto give a free-flowing off-white solid
  9. temperatureThe slurry was cooled to <15° C.
  10. filtrationfiltered

Sources & evidence

ORD record
ord-d6728d6fccc64b70bcf9687eebe646a8
Source dataset
uspto-grants-2016_03
Patent number
US09290517B2

Reaction notes

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