Diisopropylethylamine → tert-butyl 2-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-2-phenylmorpholine-4-carboxylate

HRID 272001Notes

Reaction equation

HRID 272001 reaction equation
O=[CH:2][CH2:3][C:4]1([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[O:9][CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]1.Cl.Cl.[C@@H:25]12[NH:32][C@@H:29]([CH2:30][CH2:31]1)[CH2:28][CH:27]([N:33]1[C:37]3[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=3[N:35]=[C:34]1[CH3:42])[CH2:26]2.C(N(C(C)C)CC)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:42][C:34]1[N:33]([CH:27]2[CH2:28][C@H:29]3[N:32]([CH2:2][CH2:3][C:4]4([C:17]5[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=5)[O:9][CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:5]4)[C@H:25]([CH2:31][CH2:30]3)[CH2:26]2)[C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=2[N:35]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 59835986HCID 59835986, compoundHCID 689368471-[(1R,5S)-8-azabicyclo[3.2.1]oct-3-yl]-2-methyl-1H-benzimidazole dihydrochloride

Product 1

HCID 59835967tert-butyl 2-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-2-phenylmorpholine-4-carboxylateYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 2-(2-oxoethyl)-2-phenylmorpholine-4-carboxylate (226.1 mg, 0.74 mmol), 1-[(1R,5S)8-azabicyclo[3.2.1]oct-3-yl]-2-methyl-1H-benzimidazole dihydrochloride (272.7 mg, 0.74 mmol) and diisopropylethylamine (0.27 mL, 1.48 mmol) in 3 mL CH2Cl2 was added sodium triacetoxyborohydride (235.4 mg, 1.11 mmol) and the reaction mixture was stirred for 2 h at room temperature. After evaporation, the residue was chromatographed (5% (2M NH3/MeOH) in CHCl3) to provide tert-butyl 2-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-2-phenylmorpholine-4-carboxylate (329.9 mg, 84%) as an off-white foam: 1H NMR (400 MHz, CDCl3), δ 7.65 (m, 1H), 7.49-7.40 (br., 2H), 7.39-7.34 (m, 2H), 7.31 (m, 1H), 7.27 (m, 1H), 7.19-7.11 (m, 2H), 4.75-4.16 (m, 2H), 3.76-3.47 (m, 3H), 3.40-3.13 (m, 4H), 2.58 (s, 3H), 2.46-2.32 (m, 2H), 2.17-1.82 (m 8H), 1.63 (m, 2H), 1.53-1.40 (br., 9H); ESI-MS 531 (M+H), 553 (M+Na).

Workup

  1. customAfter evaporation
  2. customthe residue was chromatographed (5% (2M NH3/MeOH) in CHCl3)

Sources & evidence

ORD record
ord-b69acf87c61c4394a608e63ba535ae95
Source dataset
uspto-grants-2008_11
Patent number
US07452992B2

Reaction notes

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