1-(Bromomethyl)-2-chloro-4-fluorobenzene → HCID 71209384, compound
Reaction equation
[C:1]([O:5][C@H:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][NH:18][C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].Br[CH2:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=1[Cl:40]>>[C:1]([O:5][C@H:6]([C:11]1[C:12]([C:21]2[CH:22]=[C:23]3[C:28](=[CH:29][CH:30]=2)[O:27][CH2:26][CH2:25][CH2:24]3)=[C:13]2[CH:20]=[CH:19][N:18]([CH2:32][C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=3[Cl:40])[C:14]2=[N:15][C:16]=1[CH3:17])[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]Participants
Conditions
- Temperature
- 40 °C
Procedure
The title compound was prepared in a manner similar to that described in Example 27, Step H from (R)-methyl 2-(tert-butoxy)-2-(4-(chroman-6-yl)-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)acetate and 1-(bromomethyl)-2-chloro-4-fluorobenzene, but finally purified on a ChiralPak ADH column (250×30 mm i.d., 5 um; ChiralTechnologies, West Chester, Pa.) under supercritical conditions maintained at 40° C., 140 bar, with MeOH modified CO2 (25% Isopropanol, 75% CO2) delivered at a combined flow rate of 90 g/min on a PIC Preplab 200 SFC system (Avignon, France). Triggered collections were made using a Knauer selectable wavelength UV-Vis detector at 230 nm (Rt=3.67 minutes): 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.49-7.42 (m, 1 H), 7.25-7.15 (m, 2 H), 7.13-7.06 (m, 2 H), 6.96-6.88 (m, 2 H), 6.30 (dd, J=3.5, 11.9 Hz, 1 H), 5.70-5.63 (m, 1 H), 5.61-5.51 (m, 2 H), 4.32-4.25 (m, 2 H), 2.95-2.79 (m, 2 H), 2.76 (d, J=1.6 Hz, 3 H), 2.15-2.04 (m, 2 H), 1.07-0.87 (s, 9 H); LC/MS (m/z) ES+=537.31 (M+1).
Workup
- customfinally purified on a ChiralPak ADH column (250×30 mm i.d., 5 um; ChiralTechnologies, West Chester, Pa.) under supercritical conditions
Sources & evidence
- ORD record
- ord-a11a22b9c56347ff80448b26cda155f0
- Source dataset
- uspto-grants-2013_12
- Patent number
- US08609653B2
Reaction notes
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