4-Methylmorpholine → 3-[4-(1-Hydroxymethyl-heptyl)-benzoylamino]-propionic acid methyl ester

HRID 658309Notes

Reaction equation

HRID 658309 reaction equation
[OH:1][CH2:2][CH:3]([C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].ClC1N=C(OC)N=C(OC)N=1.CN1CCOCC1.Cl.[CH3:38][O:39][C:40](=[O:44])[CH2:41][CH2:42][NH2:43]>ClCCl.O>[CH3:38][O:39][C:40](=[O:44])[CH2:41][CH2:42][NH:43][C:14](=[O:16])[C:13]1[CH:12]=[CH:11][C:10]([CH:3]([CH2:2][OH:1])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 2734767Methyl 3-aminopropanoate hydrochlorideHCID 674860954-(1-Hydroxymethyl-heptyl)-benzoic acid

Product 1

HCID 674855693-[4-(1-Hydroxymethyl-heptyl)-benzoylamino]-propionic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

4-(1-Hydroxymethyl-heptyl)-benzoic acid (500 mg, 2.00 mmol), 2-chloro-4,6-dimethoxy-1,3,5-triazine (362 mg, 2.06 mmol), and 4-methylmorpholine (230 μL, 2.10 mmol) are combined in anhydrous dichloromethane (10 mL) under nitrogen. The reaction is allowed to stir under nitrogen at room temperature overnight. Beta-alanine methyl ester hydrochloride (306 mg, 2.20 mmol) is added to the reaction mixture, followed by more 4-methyl morpholine (460 μL, 4.2 mmol), and allowed to stir at room temperature. Some water (<10% volume) is added to help solubility. The reaction is monitored by HPLC, and after 4 h, the reaction is diluted with more dichloromethane. The reaction is diluted with water and rinsed with 1N HCl. Upon acidification, the two layers are separated. The organic layer is washed with brine, dried over anhydrous sodium sulfate, and concentrated. The resulting residue is purified by flash column chromatography with hexanes/ethyl acetate to provide the title compound. MS (ES): 334.2 [M+H]−.

Workup

  1. stirringto stir at room temperature
  2. waitafter 4 h
  3. washrinsed with 1N HCl
  4. customUpon acidification, the two layers are separated
  5. washThe organic layer is washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe resulting residue is purified by flash column chromatography with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-39e0c476486441bf8d4cfd3eab927d6b
Source dataset
uspto-grants-2011_12
Patent number
US08076374B2

Reaction notes

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