Acetic Anhydride → HCID 59607544, compound

HRID 1945007Notes

Reaction equation

HRID 1945007 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][C@@H:15]([NH:22][C:23](=[O:30])[CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.CCN(CC)CC.[CH3:38][C:39](OC(C)=O)=[O:40]>C(Cl)Cl.O>[C:39]([NH:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][C@@H:15]([NH:22][C:23](=[O:30])[CH2:24][CH2:25][C:26]([O:28][CH3:29])=[O:27])[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1)(=[O:40])[CH3:38]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 59607780(R)-ethyl 4-(3'-aminobiphenyl-4-yl)-3-(4-methoxy-4-oxobutanamido)butanoate

Product 1

HCID 59607544HCID 59607544, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of (R)-ethyl 4-(3′-aminobiphenyl-4-yl)-3-(4-methoxy-4-oxobutanamido)butanoate (70.5 mg, 0.171 mmol), Et3N (0.027 ml, 0.205 mmol) and Ac2O (0.019 ml, 0.205 mmol) in DCM (1.7 ml) is allowed to stir at room temperature for 65 hours. The reaction mixture is diluted with water. The products are extracted with DCM in a phase separator and concentrated to give crude (98 mg). The crude is purified by silica gel flash column chromatography (eluent: DCM/MeOH=10:1) to give (R)-ethyl 4-(3′-acetamidobiphenyl-4-yl)-3-(4-methoxy-4-oxobutanamido)butanoate (71.5 mg); HPLC retention time=1.45 minutes (condition D); MS (m+1)=455.4; 1H NMR (400 MHz, CD3CN, mixture of rotamers, data for major rotamer) δ ppm 1.21 (t, J=7.1 Hz, 3H) 2.07 (s, 3H) 2.31-2.34 (m, 2H) 2.40-2.51 (m, 4H) 2.82-2.84 (m, 2H) 3.58 (s, 3H) 4.07 (q, J=7.1 Hz, 2H) 4.34-4.43 (m, 1H) 6.46 (br d, J=8.9 Hz, 1H) 7.28-7.39 (m, 4H) 7.52-7.54 (m, 3H) 7.80 (s, 1H) 8.37 (br s, 1H).

Workup

  1. extractionThe products are extracted with DCM in a phase separator
  2. concentrationconcentrated
  3. customto give crude (98 mg)
  4. customThe crude is purified by silica gel flash column chromatography (eluent: DCM/MeOH=10:1)

Sources & evidence

ORD record
ord-6d720aa555164d89848ea137ab3da754
Source dataset
uspto-grants-2013_03
Patent number
US08394853B2

Reaction notes

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