Methanol → tert-Butyl 4-(5-(tert-butoxycarbonylamino)-2-chloro-4-(methoxycarbonyl)phenyl)piperazine-1-carboxylate

HRID 1808894Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([N:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)[CH:12]=[CH:13][C:14]=1[C:15]([O:17][CH3:18])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(O)(C(F)(F)F)=O.C1C(=O)N([Cl:46])C(=O)C1.CO>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C:9]1[C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][C:12]([Cl:46])=[C:11]([N:19]2[CH2:20][CH2:21][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:23][CH2:24]2)[CH:10]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of tert-butyl 4-(3-(tert-butoxycarbonylamino)-4-(methoxycarbonyl)phenyl)piperazine-1-carboxylate (360 mg, 0.827 mmol) in DCM (4 mL) at −78° C. was added TFA (0.064 mL, 0.827 mmol). The reaction mixture was warmed to 0° C., followed by the addition of NCS (110 mg, 0.827 mmol) and MeOH (2.000 mL). The resulted reaction mixture was stirred at RT for 16 hours. The product was purified by flash chromatography (2% EtOAc/DCM, Rf 0.50) to give 150 mg (77% yield) of tert-Butyl 4-(5-(tert-butoxycarbonylamino)-2-chloro-4-(methoxycarbonyl)phenyl)piperazine-1-carboxylate. 1H-NMR (CDCl3, 400 MHz): δ 10.31 (1H, s), 8.18 (1H, s), 7.98 (1H, s), 3.90 (3H, s), 3.61 (4H, t, J=4.8 Hz), 3.14 (4H, t, J=4.8 Hz), 1.53 (9H, s), 1.49 (9H, s).

Workup

customThe resulted reaction mixture
customThe product was purified by flash chromatography (2% EtOAc/DCM, Rf 0.50)

Sources & evidence

ORD record: ord-dcd72454d8ac4e039200edd358a050e8
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362004B2

Reaction notes

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