2-Methoxybenzaldehyde → (+/-)-n-Isobutyl-4-(2-methoxybenzyl)-n-(2,3,4,5-tetrahydro-1-benzoxepin-8-ylmethyl)morpholine-2-carboxamide hydrochloride

HRID 2264170Notes

Reaction equation

HRID 2264170 reaction equation
[ClH:1].[CH2:2]([N:6]([CH2:15][C:16]1[CH:26]=[CH:25][C:19]2[CH2:20][CH2:21][CH2:22][CH2:23][O:24][C:18]=2[CH:17]=1)[C:7]([CH:9]1[O:14][CH2:13][CH2:12][NH:11][CH2:10]1)=[O:8])[CH:3]([CH3:5])[CH3:4].[CH:27](=O)[C:28]1[C:29]([O:34][CH3:35])=[CH:30][CH:31]=[CH:32][CH:33]=1.C([O-])(=O)C.[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(OCC)(=O)C>[ClH:1].[CH2:2]([N:6]([CH2:15][C:16]1[CH:26]=[CH:25][C:19]2[CH2:20][CH2:21][CH2:22][CH2:23][O:24][C:18]=2[CH:17]=1)[C:7]([CH:9]1[O:14][CH2:13][CH2:12][N:11]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[O:34][CH3:35])[CH2:10]1)=[O:8])[CH:3]([CH3:5])[CH3:4]

Participants

7

Reactant 4

HCID 86582-MethoxybenzaldehydeHCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 60209726(+/-)-N-isobutyl-N-(2,3,4,5-tetrahydro-1-benzoxepin-8-ylmethyl)morpholine-2-carboxamide hydrochloride

Product 1

HCID 60209728(+/-)-n-Isobutyl-4-(2-methoxybenzyl)-n-(2,3,4,5-tetrahydro-1-benzoxepin-8-ylmethyl)morpholine-2-carboxamide hydrochlorideYield 101.9%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 31 mg (0.080 mmol) of (±)-N-isobutyl-N-(2,3,4,5-tetrahydro-1-benzoxepin-8-ylmethyl)morpholine-2-carboxamide hydrochloride, 0.0106 mL (0.088 mmol) of o-anisaldehyde, and 6.6 mg (0.080 mmol) of sodium acetate in 0.5 mL of 1,2-dichloroethane was stirred under nitrogen at ambient temperature for 10 minutes and 19 mg (0.088 mmol) of sodium triacetoxyborohydride was added. The mixture was stirred overnight then diluted with 5 mL of ethyl acetate and washed with 2 mL each of saturated sodium bicarbonate solution, water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give 41 mg of a colorless gum. Preparative TLC (60% ethyl acetate/hexanes) gave 25 mg (68%) of product free-base as a gum. The gum was taken up in 1 mL of methanol, treated with 5 drops of 4M HCl in dioxane, and the mixture was concentrated. The residue was triturated with ether, and dried under vacuum to give the hydrochloride salt as a solid white foam. MS (m+1)=467.3; H NMR (400 MHz, CD3OD) 7.45 (m, 2H), 7.10 (m, 3H), 6.85 (m, 2H), 4.97 (m, 1H), 4.81 (m, 1H), 4.56-4.39 (m, 3H), 4.1-3.7 (m, 8H), 3.6-3.2 (m, 3H), 3.2-2.85 (m, 2H), 2.77 (d, 2H, J 6 Hz), 2.04 (m, 1H), 1.94 (m, 2H), 1.70 (m, 2H), 0.90 (m, 6H).

Workup

  1. stirringThe mixture was stirred overnight
  2. washwashed with 2 mL each of saturated sodium bicarbonate solution, water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a55f350547f24e2cba9cb50b045641b7
Source dataset
uspto-grants-2010_12
Patent number
US07855201B2

Reaction notes

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