4-Methylmorpholine → HCID 86680511, compound

HRID 1184590Notes

Reaction equation

HRID 1184590 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][NH:17][CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[OH:20][CH:21]([C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=1)[C:22](O)=[O:23].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][N:17]([C:22](=[O:23])[CH:21]([OH:20])[C:25]5[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:33])[F:34])[CH:26]=5)[CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 101658Hydroxy[3-(trifluoromethyl)phenyl]acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86680449(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazine

Product 1

HCID 86680511HCID 86680511, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the product from Example 54F (0.05 g, 0.168 mmol) and 2-hydroxy-2-(3-(trifluoromethyl)phenyl)acetic acid (0.035 g, 0.160 mmol) in anhydrous N,N-dimethylformamide (1.5 mL) was added O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.070 g, 0.185 mmol) and N-methylmorpholine (0.056 mL, 0.505 mmol). The resulting mixture was stirred at room temperature for 90 minutes and was then partitioned between water and ethyl acetate (3×). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane. The title compound was obtained as a colorless solid (73 mg, 94%). 1H NMR (300 MHz, CDCl3) δ ppm 0.87-0.99 (m, 4 H) 1.23-3.25 (m, 9H) 3.48-3.73 (m, 2 H) 4.57-4.84 (m, 2 H) 5.20-5.37 (m, 2 H) 7.45-7.64 (m, 4 H) 7.87-8.05 (m, 2 H); MS (ESI) m/z 463 (M+H)+.

Workup

  1. customwas then partitioned between water and ethyl acetate (3×)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography on silica gel using a solvent gradient of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-c26b352244854476b3c1dd85d674cdcd
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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