1-Hydroxybenzotriazole → 2-[3-chloro-4-(methylsulfonyl)phenyl]-3-[(2R,3R,7R)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]-N-methoxy-N-methylpropaneamide

HRID 1881905Notes

Reaction equation

HRID 1881905 reaction equation
Cl.[CH3:2][O:3][NH:4][CH3:5].[Cl:6][C:7]1[CH:8]=[C:9]([CH:17]([CH2:21][C@H:22]2[CH2:42][CH2:41][C:24]3([O:28][C@H:27]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C@@H:26]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[O:25]3)[CH2:23]2)[C:18]([OH:20])=O)[CH:10]=[CH:11][C:12]=1[S:13]([CH3:16])(=[O:15])=[O:14].Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C(#N)C.C(OCC)(=O)C.C(N(CC)CC)C>[Cl:6][C:7]1[CH:8]=[C:9]([CH:17]([CH2:21][C@H:22]2[CH2:42][CH2:41][C:24]3([O:28][C@H:27]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)[C@@H:26]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[O:25]3)[CH2:23]2)[C:18]([N:4]([O:3][CH3:2])[CH3:5])=[O:20])[CH:10]=[CH:11][C:12]=1[S:13]([CH3:16])(=[O:15])=[O:14]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 593314112-[3-chloro-4-(methylsulfonyl)phenyl]-3-[(2R,3R,7R)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]propanoic acid

Product 1

HCID 593315872-[3-chloro-4-(methylsulfonyl)phenyl]-3-[(2R,3R,7R)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]-N-methoxy-N-methylpropaneamideYield 69%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-methoxymethanamine hydrochloride (936 mg) in acetonitrile (40 mL) was neutralized with triethylamine (3.35 mL), and 2-[3-chloro-4-(methylsulfonyl)phenyl]-3-[(2R,3R,7R)-2,3-diphenyl-1,4-dioxaspiro[4.4]non-7-yl]propanoic acid (4.33 g), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (2.30 g) and 1-hydroxybenzotriazole (612 mg) were added under ice-cooling. The reaction mixture was stirred overnight at room temperature, diluted with ethyl acetate, and washed with water and saturated aqueous sodium hydrogen carbonate. The ethyl acetate layer was dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (3.05 g, yield 69%) was obtained as a colorless amorphous solid from a fraction eluted with ethyl acetate-hexane (3:1, volume ratio).

Workup

  1. additionwere added under ice-
  2. temperaturecooling
  3. washwashed with water and saturated aqueous sodium hydrogen carbonate
  4. dry with materialThe ethyl acetate layer was dried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-e36f0a7231014d4eb6cfcaacbed0fd58
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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