1,2-Dichloroethane → N-Fmoc-beta-alanine beta-alanine ethyl ester

HRID 219308

Reaction equation

HRID 219308 reaction equation
[C:1]([NH:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[CH2:39]([O:41][C:42](=[O:46])[CH2:43][CH2:44][NH2:45])[CH3:40].CC(N(C)C)=O>C(Cl)Cl>[C:1]([NH:18][CH2:19][CH2:20][C:21]([OH:23])=[O:22])([O:3][CH2:4][CH:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:12]2[C:17]1=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:2].[CH2:39]([O:41][C:42](=[O:46])[CH2:43][CH2:44][NH2:45])[CH3:40]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 31374DimethylacetamideHCID 757711-HydroxybenzotriazoleHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 2724630N-Fluorenylmethoxycarbonyl-I2-alanine

Product 1

HCID 86608463N-Fmoc-beta-alanine beta-alanine ethyl esterYield 96%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
23 °C

Procedure

N-Fmoc-β-alanine (311 mg, 1.0 mmol) in anhydrous CH2Cl2 (20 mL) under N2 was cooled to 0° C. HOBt (168 mg, 1.1 mmol) and EDC (230 mg, 1.2 mmol) were added and the solution was stirred for 30 min at 0° C. β-Alanine ethyl ester hydrochloride (169 mg, 1.1 mmol) in anhydrous CH2Cl2 (10 mL) and DMA (180 μL, 1.1 mmol) were added. The reaction was warmed to 23° C. and stirred for 16 h. The reaction solution was diluted with CH2Cl2 (30 mL) and washed with aqueous HCl (5%, 30 mL), followed by aqueous NaOH (0.1 M, 30 mL), and deionized H2O (30 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo. Flash column chromatography (hexanes/ethyl acetate, 1:2) afforded 5 (394 mg, 96%) as a white solid, mp 158.5-159° C.; 1H NMR (300 MHz, CDCl3) δ 7.74 (d, J=7.5 Hz, 2H), 7.58 (d, J=7.5 Hz, 2H), 7.38 (m, J=7.5 Hz, 2H), 7.29 (m, J=7.5 Hz, 2H), 6.53 (br m, 1H), 5.77 (br m, 1H), 4.34 (d, J=7.1 Hz, 2H), 4.18 (t, J=7.1 Hz, 1H), 4.11 (q, J=7.1 Hz, 2H), 3.50 (m, 4H), 2.52 (t, J=6.0 Hz, 2H), 2.40 (t, J=5.7 Hz, 2H), 1.23 (t, J=7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 172.6, 171.6, 156.7, 144.0, 141.3, 127.8, 127.1, 125.2, 120.1, 66.8, 60.9, 47.3, 37.2, 36.0, 35.0, 34.1, 14.3; IR (film) ν max 3319, 3069, 2978, 2955, 2884, 1732, 1689, 1634, 1538, 1446, 1270, 1190 cm−1; CI 411.1922 m/z (MH+, C23H27N2O5 requires 411.1920).

Workup

  1. additionwere added
  2. washwashed with aqueous HCl (5%, 30 mL)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-70f8bc4f5dae4f0a85fc186fa817b3c7
Source dataset
uspto-grants-2012_06
Patent number
US08198230B2

Linked notes

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