Water → (R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate

HRID 546148Notes

Reaction equation

HRID 546148 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C@@H:12](CC2CCCC2)[C:13](NC2C=CN(CCC(O)=O)N=2)=[O:14])C=CC=1S(C)(=O)=O.C(N(CC)CC)C.[C:39]1([CH3:49])[CH:44]=[CH:43][C:42]([S:45](Cl)(=[O:47])=[O:46])=[CH:41][CH:40]=1.[OH2:50]>C(Cl)Cl>[O:14]1[CH2:13][CH2:12][CH2:4][C@@H:3]1[CH2:2][O:46][S:45]([C:42]1[CH:43]=[CH:44][C:39]([CH3:49])=[CH:40][CH:41]=1)(=[O:50])=[O:47]

Participants

6

Reactant 4

HCID 962WaterHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 671905033-{3-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazol-1-yl}-propionic acid

Product 1

HCID 7033050(R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonateYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

In a round bottom flask was placed (R)-(tetrahydro-furan-2-yl)-methanol (prepared as in PCT WO 2003/095438 A1, Example 3, 4.65 g, 45.5 mmol), methylene chloride (100 mL) and triethylamine (8.4 mL, 60.6 mmol) and it was cooled to 0° C. To this cooled solution was then added a solution of p-toluenesulfonyl chloride (10.4 g, 54.6 mmol) in methylene chloride (30 mL) dropwise. Once the addition was complete the reaction was then warmed to 25° C. and stirred for 16 h. The reaction was then diluted with water (50 mL) and extracted with methylene chloride (3×30 mL). The combined organic extracts were then dried over sodium sulfate, filtered and concentrated in vacuo. Purification on an AnaLogix Intelliflash system (80 g column, 3% ethyl acetate/hexanes to 40% ethyl acetate/hexanes) afforded toluene-4-sulfonic acid tetrahydro-furan-2(R)-ylmethyl ester (8.37 g, 72%) as a clear colorless oil: [α]32589=−14.4° (c=0.72, methylene chloride); ES-HRMS m/e calcd for C12H16O4S (M+H)+ 257.0842, observed 257.0841; 1H NMR (300 MHz, CDCl3) δ ppm 1.95-2.08 (m, 1H, CH of CH2), 2.14-2.40 (m, 3H, CH2 and CH of CH2), 4.02-4.19 (m, 2H, OCH2), 4.29-4.49 (m, 3H, OCH and OCH2), 7.69 (d, J=8.0 Hz, 2H, Ar), 8.15 (d, J=8.0 Hz, 2H, Ar).

Workup

  1. customIn a round bottom flask was placed
  2. additionOnce the addition
  3. extractionextracted with methylene chloride (3×30 mL)
  4. dry with materialThe combined organic extracts were then dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification on an AnaLogix Intelliflash system (80 g column, 3% ethyl acetate/hexanes to 40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-6cbe558b364a4289adbbba2cf4727b0c
Source dataset
uspto-grants-2011_05
Patent number
US07935699B2

Reaction notes

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