4-Toluenesulfonyl chloride → HCID 59504841, compound

HRID 1496939Notes

Reaction equation

HRID 1496939 reaction equation
[F:1][C:2]1([F:8])[CH2:5][CH:4]([CH2:6][OH:7])[CH2:3]1.C(N(CC)CC)C.[CH3:16][C:17]1[CH:22]=[CH:21][C:20]([S:23](Cl)(=[O:25])=[O:24])=[CH:19][CH:18]=1>CN(C)C1C=CN=CC=1.C(Cl)Cl.O>[CH3:16][C:17]1[CH:22]=[CH:21][C:20]([S:23]([O:7][CH2:6][CH:4]2[CH2:5][C:2]([F:8])([F:1])[CH2:3]2)(=[O:25])=[O:24])=[CH:19][CH:18]=1

Participants

7

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 45480377(3,3-Difluorocyclobutyl)methanol

Product 1

HCID 59504841HCID 59504841, compoundYield 97.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (3,3-difluorocyclobutyl)methanol (500 mg, 4.09 mmol, 1.00 equiv), triethylamine (662.6 mg, 6.55 mmol, 1.60 equiv), and 4-dimethylaminopyridine (750 mg, 6.14 mmol, 1.50 equiv) in CH2Cl2 (5 mL) under argon at 0° C. was added 4-methylbenzene-1-sulfonyl chloride (1.01 g, 5.30 mmol, 1.30 equiv) in portions. The resulting mixture was stirred overnight at ambient temperature. The mixture was then diluted with H2O (20 mL) and extracted with EtOAc (3×20 mL). The combined organic layers were dried with anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified using flash column chromatography (silica gel, EtOAc/Hexanes (1:5)) to yield 1.1 g (97%) of a light yellow oil. 1H-NMR (300 MHz, CDCl3): δ ppm 7.77 (d, J=7.6 Hz, 2H), 7.34 (d, J=8.0 Hz, 2H), 4.03 (d, J=6.5 Hz, 2H), 2.75-2.50 (m, 2H), 2.50-2.36 (m, 4H), 2.36-2.08 (m, 2H).

Workup

  1. extractionextracted with EtOAc (3×20 mL)
  2. dry with materialThe combined organic layers were dried with anhydrous Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe crude residue was purified

Sources & evidence

ORD record
ord-da659c9cb2d34c1b834fbb5cc3f97ffc
Source dataset
uspto-grants-2015_12
Patent number
US09199945B2

Reaction notes

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