Dichloromethane → Ammonia dichloromethane

HRID 33712Notes

Reaction equation

HRID 33712 reaction equation
[N:1]1([CH2:7][CH2:8][CH2:9][O:10][C:11]2[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[N:25]([CH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)[CH2:24][CH2:23]2.C(O)(C(F)(F)F)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+].[CH2:58]([Cl:60])[Cl:59]>>[NH3:1].[CH2:58]([Cl:60])[Cl:59].[Br:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[N:25]([CH:29]1[CH2:34][CH2:33][N:32]([CH2:15][C:14]3[CH:17]=[CH:18][C:11]([O:10][CH2:9][CH2:8][CH2:7][N:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:12][CH:13]=3)[CH2:31][CH2:30]1)[CH2:24][CH2:23]2

Participants

8

Reactant 6

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 14798Sodium HydroxideHCID 27663244-(3-Piperidin-1-ylpropoxy)benzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 22028305HCID 22028305, compound

Product 2

HCID 102078095-Bromo-1-{1-[4-(3-piperidin-1-yl-propoxy)-benzyl]-piperidin-4-yl}-2,3-dihydro-1H-indoleHCID 22731429Ammonia dichloromethaneYield 1%

Procedure

A solution of the product of Example 9 (93 mg) and 5-bromo-1-piperidin-4-yl-2,3-dihydro-1H-indole*2 TFA (191 mg) in DCM (2 mL) was treated with sodium triacetoxyborohydride (150 mg). After 16 h, the resulting mixture was treated with 10% sodium hydroxide (5 mL) and extracted with DCM (3×10 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Chromatography of the residue (1-5% 2 M methanolic ammonia/DCM) gave the title compound as a colorless oil (79 mg). 1H NMR (400 MHz, CDCl3): 7.20 (d, J=8.6 Hz, 2H), 7.11-7.07 (m, 2H), 6.84 (d, J=8.6 Hz, 2H), 6.23 (d, J=9.1 Hz, 1H), 4.00 (t, J=6.1 Hz, 2H), 3.46 (s, 2H), 3.37 (7, J=8.3 Hz, 2H), 3.28 (m, 1H), 2.97 (m, 2H), 2.90 (t, J=8.3 Hz, 2H), 2.54 (m, 2H), 2.47 (br, 4H), 2.06-1.97 (m, 4H), 1.75-1.60 (m, 8H), 1.50-1.43 (m, 2H).

Workup

  1. extractionextracted with DCM (3×10 mL)
  2. dry with materialThe combined organic phases were dried (sodium sulfate)
  3. customevaporated

Sources & evidence

ORD record
ord-c6994694cdb54e6a86c77bb0fad7ae68
Source dataset
uspto-grants-2008_09
Patent number
US07429586B2

Reaction notes

Loading…