Triethylamine → HCID 86670197, compound

HRID 1038955Notes

Reaction equation

HRID 1038955 reaction equation
[ClH:1].[CH2:2]([O:4][C:5](=[O:9])[C@H:6]([CH3:8])[NH2:7])[CH3:3].[P:10](Cl)(Cl)([O:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:11].C(N(CC)CC)C.C(OCC)(=O)C>ClCCl.CCCC(C)C>[Cl:1][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[O:12][P:10](=[N:7][C@@H:6]([CH3:8])[C:5]([O:4][CH2:2][CH3:3])=[O:9])=[O:11]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl Acetate2×HCID 13038Phosphorodichloridic acid, phenyl esterHCID 2724356L-Alanine, ethyl ester, hydrochloride (1:1)

Product 1

HCID 86670197HCID 86670197, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 78922-MethylpentaneSolvent2×

Procedure

To a stirred solution of L-Alanine ethyl ester hydrochloride salt (5 g, 32.5 mmol, dried in vaccum for 48 h) in dichloromethane (50 mL) at approx -78° C. was dropwise added a solution of phenyl dichlorophosphate (5.7 g, 27 mmol, 4.05 ml) in dichloromethane (20 ml) over 5 minutes. To the resulting solution was added a solution of triethylamine (8.2 g, 81 mmol, 11.3 mL) in dichloromethane (20 mL) during 30 min. The obtained solid was slowly allowed to reach room temperature over 2 h, then the reaction mixture was applied directly onto column. Column chromatography (diam: 7 cm, SiO2: 100 g, Packing eluent: ethyl acetate in i-Hexane 20%) of the residue using ethyl acetate in i-Hexane (stepwise gradient 20-30%) gave separation from byproducts such as phosphordiamidates. Appropriate fractions (monitored by TLC: i-Hex-EtOAc 3:2, product comes first as baseline spots, followed by diamidates which migrates on the TLC plate) were concentrated giving (2S)-ethyl 2-(chloro(phenoxy)phosphorylamino)-propanoate, a colorless oil (2.16 g, 7.4 mmol, 27%). The product was diluted with dichloromethane into a 0.25 M stock solution and could be kept in the freezer for up to a month. NMR data (400 MHz, 298 K, CDCl3): 1 H, δ 1.23-1.37 (m, 3 H), 1.52 (2d, 3 H), 4.08-4.37 (m, 4 H), 7.21-7.29 (m, 3 H), 7.37 (m, 2 H). 31P, δ 7.60 and 7.96 (2s, no P standard used).

Workup

  1. customgave
  2. customseparation from byproducts such as phosphordiamidates
  3. concentrationwere concentrated

Sources & evidence

ORD record
ord-adb638b0edbd4e139d7e91228addfcab
Source dataset
uspto-grants-2013_10
Patent number
US08552021B2

Reaction notes

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