Stannous chloride dihydrate → 1-(3-Amino-4-Methylphenyl)Ethanone

HRID 2407593

Reaction equation

O.O.[Sn](Cl)Cl.[CH3:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([CH3:15])=[O:14])=[CH:9][C:8]=1[N+:16]([O-])=O>CO>[NH2:16][C:8]1[CH:9]=[C:10]([C:13](=[O:14])[CH3:15])[CH:11]=[CH:12][C:7]=1[CH3:6]

Participants

Conditions

Temperature: 60 °C

Procedure

Tin(II)dichloride dihydrate (37 g, 168 mmol) was added to 4-methyl-3-nitroacetophenone (10 g, 56 mmol) dissolved in methanol (350 mL). The reaction mixture was heated at 60° C. for 18 h, concentrated, and dried under high vacuum to give to 1-(3-amino-4-methylphenyl)ethanone which contained tin salts. LC (Cond.-J1): 0.73 min; LC/MS: Anal. Calcd. for [M+H]+ C9H11NO: 150.08; found: 150. The material was used without purification. HATU (10.6 g, 28 mmol) was added in one portion to a stirred solution of 1-(3-amino-4-methylphenyl)ethanone (4.1 g, 28 mmol), N-Boc-L-proline (6 g, 28 mmol), and Hunig's base (25 mL) in DMF (225 mL) and the reaction mixture was stirred 18 h. The solvent was removed in vacuo and the residue was taken up in ethyl acetate/methanol (1:1) and applied to a flash SiO2 column. A step elution by gradient 20%; 50%; 75%; 100% B (total elution vol 1500 mL); A=hexanes; B=ethyl acetate; and a final elution with; 10% methanol/ethyl acetate was conducted to give J.38, 4.4 g (46%). 1H NMR (300 MHz, DMSO-d6) δ: 9.51/9.45 (s, 1H), 7.95-7.92 (m, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.37 (d, J=7.7 Hz, 1H), 4.33-4.29 (m, 1H), 3.48-3.29 (m, 2H), 2.50 (s, 3H), 2.26 (s, 3H), 1.98-1.80 (m, 4H), 1.41/1.36 (m, 9H). LC (Cond.-J1): 1.70 min; LRMS: Anal. Calcd. for [M+H]+ C19H27N2O4: 347.20; found 347.41.

Workup

concentrationconcentrated
customdried under high vacuum

Sources & evidence

ORD record: ord-cdbb6b327e194753a9176c9830484051
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809548B2

Linked notes

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