Water → [(2R)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate

HRID 1259457Notes

Reaction equation

HRID 1259457 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH2:11][C@H:10]([CH2:13][OH:14])[O:9][C:8]=2[CH:15]=1)([O-:3])=[O:2].[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.O>N1C=CC=CC=1>[CH3:26][C:16]1[CH:21]=[CH:20][C:19]([S:22]([O:14][CH2:13][C@@H:10]2[O:9][C:8]3[CH:15]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=[CH:6][C:7]=3[O:12][CH2:11]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 962WaterHCID 73974-Toluenesulfonyl chlorideHCID 25019919[(2S)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methanol

Product 1

HCID 59456452[(2R)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonateYield 81.1%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

A 500 mL three necked flask equipped with a magnetic stir bar and thermocouple and the pyridine solution of [(2S)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methanol (˜66.4 mmol) from Example 1H is immersed in an ice/brine bath to achieve an internal temperature of 0-1° C. p-toluenesulfonyl chloride (14.55 g, 76.3 mmol) is dissolved in pyridine (17 mL) and the resulting solution is added over 20 min. The mixture is stirred while allowing the bath to expire, and then for 18 h. Water (180 mL) is added at a continuous rate over 30 min. The suspension is stirred for 1 h, and then collected by vacuum filtration onto a medium porosity fritted funnel. The filter cake is washed with water (160 mL) and suction dried under nitrogen to give [(2R)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate (19.68 g, 81% two steps) as a brown solid; m.p. 138° C. LCMS (Standard Method): 2.78 min, 388 (M+Na)+. 1H NMR (300 MHz, DMSO-d6) δ7.79-7.72 (m, 3H), 7.49-7.42 (m, 3H), 7.06 (d, J=8.8 Hz, 1H), 4.59-4.55 (m, 1H), 4.41 (dd, J=2.6, 11.6 Hz, 2H), 4.22 (dd, J=6.3, 11.5 Hz, 1H), 4.12 (dd, J=6.8, 11.7 Hz, 1H) 2.38 (s, 3H).

Workup

  1. additionthe resulting solution is added over 20 min
  2. stirringThe suspension is stirred for 1 h
  3. filtrationcollected by vacuum filtration onto a medium porosity fritted funnel
  4. washThe filter cake is washed with water (160 mL) and suction
  5. customdried under nitrogen

Sources & evidence

ORD record
ord-3048f8f1b17743e9ad8cd5c8a6e114fa
Source dataset
uspto-grants-2013_06
Patent number
US08466296B2

Reaction notes

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