1-Chloroethyl chloroformate → 3-(2,8-Bis(trifluoromethyl)-4-quinolinyl)-3-azetidinol

HRID 1370331Notes

Reaction equation

[F:1][C:2]([F:36])([F:35])[C:3]1[CH:12]=[C:11]([C:13]2([OH:30])[CH2:16][N:15](C(C3C=CC=CC=3)C3C=CC=CC=3)[CH2:14]2)[C:10]2[C:5](=[C:6]([C:31]([F:34])([F:33])[F:32])[CH:7]=[CH:8][CH:9]=2)[N:4]=1.ClC(OC(Cl)C)=O>ClC(Cl)C>[F:36][C:2]([F:1])([F:35])[C:3]1[CH:12]=[C:11]([C:13]2([OH:30])[CH2:16][NH:15][CH2:14]2)[C:10]2[C:5](=[C:6]([C:31]([F:32])([F:33])[F:34])[CH:7]=[CH:8][CH:9]=2)[N:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of 3-(2,8-bis(trifluoromethyl)-4-quinolinyl)-1-diphenylmethyl-3-azetidinol (690 mg, 1.37 mmol) in dichloroethane (20 mL), at 0° C., was added dropwise 1-chloroethyl chloroformate (0.18 mL, 1.2 eq). The mixture was stirred at 70° C. for 1 h and concentrated in vacuo. The residue was dissolved in MeOH (20 mL), stirred at room temperature for 17 h, concentrated in vacuo and the residue triturated with ether to give the title compound (351 mg, 69%) as a pale-yellow solid: mp 201° C. (dec); NMR δH (400 MHz, CDCl3) 4.44-4.45 (2H, m), 4.76-4.78 (2H, m), 7.95-7.99 (1H, m), 8.23 (1H, s), 8.38-8.42 (2H, m), 9.00 (1H, br s), 9.47 (1H, br s); Anal. Calcd for C14H11ClF6N2O: C, 45.12; H, 2.97; N, 7.51. Found: C, 45.21; H, 3.29; N, 7.08.

Workup

concentrationconcentrated in vacuo
dissolutionThe residue was dissolved in MeOH (20 mL)
stirringstirred at room temperature for 17 h
concentrationconcentrated in vacuo
customthe residue triturated with ether

Sources & evidence

ORD record: ord-6907f66e4420444b8a4a384d3b4d8fbf
Source dataset: uspto-grants-2003_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06583156B1

Reaction notes

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