tert-Butanol → HCID 67538549, compound
Reaction equation
C([N:3]([CH2:6][CH3:7])[CH2:4]C)C.[CH2:8]([O:10][C:11](=[O:26])[C:12]([C:19]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=1)([F:18])CCC(O)=O)[CH3:9].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:34])C=CC=CC=1.[CH3:44][C:45]([OH:48])([CH3:47])[CH3:46]>>[CH2:8]([O:10][C:11](=[O:26])[C:12]([C:19]1[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=1)([F:18])[CH2:7][CH2:6][NH:3][C:4]([O:48][C:45]([CH3:47])([CH3:46])[CH3:44])=[O:34])[CH3:9]Participants
Conditions
- Temperature
- 95 °C
Procedure
Triethylamine (0.53 mL, 3.81 mmol) was added to a solution of 2-(4-chlorophenyl)-2-fluoro-pentanedioic acid 1-ethyl ester (1.00 g, 3.46 mmol) in t-BuOH (20 mL) followed by the addition of diphenylphosphoryl azide (0.82 mL, 3.81 mmol). The mixture was heated at 95° C. for 3 hours, concentrated in vacuo, and partitioned between dilute aqueous NaHCO3 and DCM. The separated DCM layer was dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was chromatographed (SiO2) using DCM as eluent to give 4-tert-butoxycarbonylamino-2-(4-chlorophenyl)-2-fluoro-butyric acid ethyl ester (600 mg). 1H NMR (CDCl3, 400 MHz) δ 7.42 (m, 2H), 7.35 (m, 2H), 5.25 (m, 0.4H), 4.61 (m, 0.6H), 4.19 (m, 2H), 3.35 (m, 0.6H), 3.23 (m, 1.4H), 2.59 (m, 1H), 2.34 (m, 1H), 1.40 (m, 9H), 1.24 (m, 3H). LCMS (APCI+) m/z 260 [M+H]+(loss of Boc group).
Workup
- concentrationconcentrated in vacuo
- custompartitioned between dilute aqueous NaHCO3 and DCM
- dry with materialThe separated DCM layer was dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe crude product was chromatographed (SiO2)
Sources & evidence
- ORD record
- ord-d7fee96e67d34fbea73993af7da40e34
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08680114B2
Reaction notes
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