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

HRID 1259456Notes

Reaction equation

HRID 1259456 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 98%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

A 5 L three necked flask equipped with a mechanical stirrer and thermocouple is changed with [(2S)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methanol (210.4 g, 0.996 mol) and anhydrous pyridine (600 mL). The flask is immersed in an ice/brine bath to achieve an internal temperature of 0-1° C. To this is added a solution of p-toluenesulfonyl chloride (220.0 g, 1.15 mol) is dissolved in pyridine (200 mL) over 30 min. The bath is allowed to expire, and the mixture is stirred for 18 h at room temperature. Water (1600 mL) is added at a constant rate over 45 min. The resulting suspension is stirred for 1 h, and then the precipitate is collected by vacuum filtration onto a medium porosity fritted funnel. The filter cake is washed with water (1600 mL) and suction dried under nitrogen to give [(2R)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate (356.8 g, 98%) as a tan powder; 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. customThe flask is immersed in an ice/brine bath
  2. customan internal temperature of 0-1° C
  3. stirringThe resulting suspension is stirred for 1 h
  4. filtrationthe precipitate is collected by vacuum filtration onto a medium porosity fritted funnel
  5. washThe filter cake is washed with water (1600 mL) and suction
  6. customdried under nitrogen

Sources & evidence

ORD record
ord-1b6483995e3644b1a6554b5edbca15da
Source dataset
uspto-grants-2013_06
Patent number
US08466296B2

Reaction notes

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