Propylphosphonic anhydride → Methyl 4-(3-chloro-5-isopropoxy-4-methoxybenzamido)-2-methylbenzoate

HRID 62747Notes

Reaction equation

Cl[C:2]1C=C(C=C(OC(C)C)C=1OC)C(O)=O.[CH2:17]([O:24][C:25]1[C:43]([O:44][CH:45]2[CH2:50]CCC[CH2:46]2)=[CH:42][C:28]([C:29]([NH:31][C:32]2[CH:41]=[CH:40][C:35]([C:36]([O:38][CH3:39])=[O:37])=[CH:34][CH:33]=2)=[O:30])=[CH:27][C:26]=1[Cl:51])C1C=CC=CC=1.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CCOC(C)=O.C(Cl)Cl>[Cl:51][C:26]1[CH:27]=[C:28]([CH:42]=[C:43]([O:44][CH:45]([CH3:46])[CH3:50])[C:25]=1[O:24][CH3:17])[C:29]([NH:31][C:32]1[CH:33]=[CH:34][C:35]([C:36]([O:38][CH3:39])=[O:37])=[C:40]([CH3:2])[CH:41]=1)=[O:30]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 3-chloro-5-isopropoxy-4-methoxybenzoic acid (5) (250 mg, 1.02 mmol), methyl 4-amino-2-methylbenzoate (6) (177 mg, 1.07 mmol) and TEA (150 μL, 1.07 mmol) in EtOAc (2.5 mL) was treated with T3P (50% in EtOAc) (1.63 mL, 2.55 mmol) and the mixture was heated at 60° C. for 5 h. The mixture was diluted with DCM (5 mL) and washed with 1M HCl (5 mL) followed by satd. NaHCO3 solution (5 mL). The organic solvents were removed in vacuo and the residue purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane to yield methyl 4-(3-chloro-5-isopropoxy-4-methoxybenzamido)-2-methylbenzoate (7) (167 mg, 40%): m/z 392 [M+H]+ (ES+), 390 [M−H]− (ES−). 1H NMR (400 MHz, CDCl3) δ:7.98 (1H, d), 7.78 (1H, s), 7.59-7.50 (2H, m), 7.40 (2H, dd), 4.67 (1H, sep), 3.94 (3H, s), 3.89 (3H, s), 2.62 (3H, s), 1.40 (6H, d).

Workup

washwashed with 1M HCl (5 mL)
customThe organic solvents were removed in vacuo
customthe residue purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane

Sources & evidence

ORD record: ord-91d471fa7af5481aa6e1236715a8cbd7
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09447028B2

Reaction notes

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