Chloromethyl Methyl Ether → Glycine tert-butyl ester hydrochloride

HRID 554808Notes

Reaction equation

HRID 554808 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:38][CH3:39])=[C:6]([CH:37]=1)[CH2:7][CH:8]1[C:14](=[O:15])[N:13]([C:16]([NH:18][C@H:19]([CH2:34][CH3:35])[C:20]([NH:22][C:23]2[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=2[O:32]C)[C:26]([OH:28])=[O:27])=[O:21])=[O:17])[CH2:12][C:11](=[O:36])[NH:10][CH2:9]1.OC1C=C[C:44]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])=CC=1[N+]([O-])=O.ClCOC.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C.C(Cl)Cl>[ClH:1].[C:48]([O:47][C:45](=[O:46])[CH2:44][NH2:10])([CH3:51])([CH3:50])[CH3:49].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:38][CH3:39])=[C:6]([CH:37]=1)[CH2:7][CH:8]1[C:14](=[O:15])[N:13]([C:16]([NH:18][C@H:19]([CH2:34][CH3:35])[C:20]([NH:22][C:23]2[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=2[OH:32])[C:26]([OH:28])=[O:27])=[O:21])=[O:17])[CH2:12][C:11](=[O:36])[NH:10][CH2:9]1

Participants

8

Reactant 4

HCID 7864Chloromethyl Methyl EtherHCID 81531DiisopropylethylamineHCID 22667857Tert-butyl 4-hydroxy-3-nitrobenzoateHCID 576710433-{[(2r)-2-({[6-(5-Chloro-2-methoxybenzyl)-3,7-dioxo-1,4-diazepan-1-yl]carbonyl}amino)butanoyl]amino}-4-methoxybenzoic acid

Product 2

HCID 2725036Glycine tert-butyl ester hydrochlorideHCID 576711093-{[(2R)-2-({[6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-1,4-diazepan-1-yl]carbonyl}amino)butanoyl]amino-}-4-hydroxybenzoic acid

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the synthesis intermediate of Example 265, that is, tert-butyl 4-hydroxy-3-nitrobenzoate (0.42 g), methylene chloride (10 ml), chloromethylmethylether (0.16 ml), and N,N-diisopropylethylamine (0.37 ml) were added under ice cooling and the mixture was stirred at room temperature for 2 hours. The reaction solution was diluted with ethyl acetate and successively washed with water, a potassium hydrogensulfate aqueous solution, and saturated saline. The mixture was dried over with anhydrous magnesium sulfate, then concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1). To the obtained tert-butyl 4-methoxymethyloxy-3-nitrobenzoate (0.26 g), ethanol (10 ml) and 10% palladium carbon (40 mg) were added and the mixture was stirred under hydrogen atmosphere at room temperature for 7 hours. The reaction solution was filtered, the filtrate was concentrated, and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=6/1 to 1/1). The obtained tert-butyl 3-amino-2-methoxymethyloxybenzoate was used, instead of the starting material compound of Example 220, that is, the glycine tert-butyl ester hydrochloride, for the similar procedure as in Example 220 and Example 245 to obtain the title compound.

Workup

  1. washsuccessively washed with water
  2. dry with materialThe mixture was dried over with anhydrous magnesium sulfate
  3. concentrationconcentrated
  4. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1)
  5. additionTo the obtained tert-butyl 4-methoxymethyloxy-3-nitrobenzoate (0.26 g), ethanol (10 ml) and 10% palladium carbon (40 mg) were added
  6. stirringthe mixture was stirred under hydrogen atmosphere at room temperature for 7 hours
  7. filtrationThe reaction solution was filtered
  8. concentrationthe filtrate was concentrated
  9. customthe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=6/1 to 1/1)

Sources & evidence

ORD record
ord-8f4446d74538422a87b7936293383981
Source dataset
uspto-grants-2011_11
Patent number
US08049006B2

Reaction notes

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