Boron Trichloride → HCID 67089891, compound

HRID 2074419Notes

Reaction equation

HRID 2074419 reaction equation
[NH2:1][CH2:2][C@H:3]1[C:12]2[C:7](=[C:8]([O:14]C)[C:9]([CH3:13])=[CH:10][CH:11]=2)[CH2:6][C@@H:5]([CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH:24]([NH:26][C:27](=[O:35])[C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[CH3:25])[CH2:18][CH2:17]2)[O:4]1.B(Cl)(Cl)[Cl:37]>ClCCl>[ClH:34].[ClH:37].[NH2:1][CH2:2][C@H:3]1[C:12]2[C:7](=[C:8]([OH:14])[C:9]([CH3:13])=[CH:10][CH:11]=2)[CH2:6][C@@H:5]([CH:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH:24]([NH:26][C:27](=[O:35])[C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[CH3:25])[CH2:18][CH2:17]2)[O:4]1

Participants

4

Reactant 2

HCID 25135Boron TrichlorideHCID 67090018HCID 67090018, compound

Product 1

HCID 67089891HCID 67089891, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

Cool a solution of N-{3-[4-((1R,3S)-1-aminomethyl-5-methoxy-6-methyl-isochroman-3-yl)-piperidin-1-yl]-1-methyl-propyl}-4-chloro-benzamide in anhydrous dichloromethane (4 mL) to −20° C., and add 6 equivalents of BCl3 (using 1M BCl3 in dichloromethane) slowly into the solution. Following complete addition, stir the reaction mixture at −20° C. for 2 hours and 0° C. for 1 hour. Cool again to −20° C. and quench with anhydrous CH3OH (0.5 mL). Allow the resulting solution to warm to room temperature and concentrate. Purify the crude product on a 2 g SCX column and then by chromatography on a 1 g silica gel column (eluted by 7N NH3 in methanol:ethyl acetate=1:10). Collect the appropriate fractions, concentrate and convert to the title compound with 2M HCl in diethyl ether. CIMS 486.2, tR (min)=2.30.

Workup

  1. additionaddition
  2. wait0° C. for 1 hour
  3. temperatureCool again to −20° C.
  4. customquench with anhydrous CH3OH (0.5 mL)
  5. temperatureto warm to room temperature
  6. concentrationconcentrate
  7. customPurify the crude product on a 2 g SCX column
  8. washby chromatography on a 1 g silica gel column (eluted by 7N NH3 in methanol:ethyl acetate=1:10)
  9. customCollect the appropriate fractions
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-c4aabcdd4c4c4294a9941bb19de031c3
Source dataset
uspto-grants-2011_04
Patent number
US07919508B2

Reaction notes

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