Hydrochloric Acid → HCID 58928334, compound

HRID 851953Notes

Reaction equation

HRID 851953 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[N:14]3[CH2:15][CH2:16][N:17]([C:19]([C:21]4[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=4)=[O:20])[CH2:18][C@@H:13]3[CH2:12][CH2:11][CH2:10]2)=[C:5]([CH3:31])[C:4]=1[CH3:32].Cl>C(Cl)Cl>[OH:2][C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[N:14]3[CH2:15][CH2:16][N:17]([C:19]([C:21]4[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=4)=[O:20])[CH2:18][C@@H:13]3[CH2:12][CH2:11][CH2:10]2)=[C:5]([CH3:31])[C:4]=1[CH3:32]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 58928351HCID 58928351, compound

Product 1

HCID 58928334HCID 58928334, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-70 °C

Procedure

A CH2Cl2 solution of [(6R,9aS)-6-(4-methoxy-2,3-dimethylphenyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-methanone obtained in step 5 (2.30 g, 5.14 mmoles) is treated with 15.4 mL of HCl (1 M in Et2O) and allowed to stand for 10 min. This solution is concentrated in vacuo and then dissolved in 70 mL anhydrous CH2Cl2. This solution is cooled to −70° C. (dry ice/isopropanol bath) under nitrogen and treated with BBr3 (1 M in DCM, 20.6 mL) dropwise via syringe over 20 mins. The mixture is stirred for 18 h while warming to ambient temperature. After this time, the mixture is cooled to 0° C., treated with 150 mL saturated NaHCO3 and stirred vigorously for 30 min. The phases are separated and the aqueous phase is extracted three times with CH2Cl2. The combined extracts are dried over Na2SO4, filtered and concentrated in vacuo to afford [(6R,9aS)-6-(4-hydroxy-2,3-dimethylphenyl)-octahydro-pyrido[1,2-a]pyrazin-2-yl]-(6-trifluoromethyl-pyridin-3-yl)-methanon as a light brown solid which is used without additional purification. LC/MS: 434 (M+1). 1H NMR (mixture of rotamers, 400 MHz, CDCl3): 8.74 (1H, d), 7.94 (1H, dd), 7.88 (1H, dd), 7.22 (1H, dd), 6.64 (1H, dd), 4.92 (1H, bs), 4.50 (1H, dd), 3.41-3.30 (2H, bm), 3.21 (1H, m), 3.03 (1H, m), 2.91-2.53 (3H, bm), 2.25-2.14 (6H, m), 1.92-1.58 (5H, bm), 1.20-1.32 (3H, bm).

Workup

  1. concentrationThis solution is concentrated in vacuo
  2. dissolutiondissolved in 70 mL anhydrous CH2Cl2
  3. additiontreated with BBr3 (1 M in DCM, 20.6 mL) dropwise via syringe over 20 mins
  4. temperaturewhile warming to ambient temperature
  5. temperatureAfter this time, the mixture is cooled to 0° C.
  6. additiontreated with 150 mL saturated NaHCO3
  7. stirringstirred vigorously for 30 min
  8. customThe phases are separated
  9. extractionthe aqueous phase is extracted three times with CH2Cl2
  10. dry with materialThe combined extracts are dried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a0849d06835c4992837534df826add73
Source dataset
uspto-grants-2007_08
Patent number
US07253168B2

Reaction notes

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