Triethylamine → (1S)-1-(2,6-Dichloro-3-fluorophenyl)ethyl methanesulfonate
Reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@@H:10]([OH:12])[CH3:11].C(N(CC)CC)C.[CH3:20][S:21](Cl)(=[O:23])=[O:22]>C1(C)C=CC=CC=1.O>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@@H:10]([O:12][S:21]([CH3:20])(=[O:23])=[O:22])[CH3:11]Participants
Conditions
- Temperature
- 2.5 °C
Procedure
To a cooled (ice bath) solution of (S)-1-(2,6-Dichloro-3-fluorophenyl)ethanol (4.00 g, 16.3 mmol) and triethylamine (3.4 mL, 24 mmol) in toluene (20 mL) was added dropwise methanesulfonyl chloride (1.64 mL, 21.1 mmol). A white suspension formed that was stirred at 0-5° C. for 35 min. The reaction mixture was diluted with H2O (20 mL), the layers were separated, and the aqueous layer was extracted with toluene (10 mL). The combined organic layers were washed with water (2×10 mL) and concentrated under vacuum at 40-45° C. to give the title compound as colorless oil containing ≈0.2 eq. of toluene according to 1H NMR. This material was used directly in the next step. 1H NMR (CDCl3, 400 MHz): δ=7.33 (dd, J=9.0, 4.9 Hz, 1H), 7.12 (dd, J=9.0, 8.0 Hz, 1H), 6.45 (q, J=6.8 Hz, 1H), 2.91 (s, 3H), 1.84 (d, J=6.8 Hz).
Workup
- customA white suspension formed
- customthe layers were separated
- extractionthe aqueous layer was extracted with toluene (10 mL)
- washThe combined organic layers were washed with water (2×10 mL)
- concentrationconcentrated under vacuum at 40-45° C.
Sources & evidence
- ORD record
- ord-58a7cbbf30ba415b839eeb097bedf830
- Source dataset
- uspto-grants-2011_09
- Patent number
- US08022206B2
Reaction notes
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