Pyridine → HCID 178453973, compound

HRID 1257707Notes

Reaction equation

HRID 1257707 reaction equation
[C:1]([O:5][C:6](=[O:16])[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][OH:15])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[CH3:23][S:24](Cl)(=[O:26])=[O:25]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:7][C@H:8]1[CH2:9][CH2:10][C@H:11]([CH2:14][O:15][S:24]([CH3:23])(=[O:26])=[O:25])[CH2:12][CH2:13]1)=[O:16])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 178453956HCID 178453956, compound

Product 1

HCID 178453973HCID 178453973, compoundYield 90.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Trans (4-hydroxymethyl-cyclohexyl)-carbamic acid tert-butyl ester (3.49 g, 15.0 mmol) in DCM (50 mL) was treated with pyridine (4.98 mL, 60.8 mmol). The mixture was cooled to 0° C. and methanesulfonyl chloride (2.36 mL, 30.4 mmol) was added dropwise over 5 minutes. The mixture was stirred at room temperature for 5 hours. The mixture was then concentrated under vacuum. The residue was partitioned between ethyl acetate and water and the aqueous phase was extracted with ethyl acetate (×2). The combined organic extracts were washed with brine, dried with sodium sulfate and concentrated under vacuum. The residue was triturated with cyclohexane then dried under vacuum to give a white solid. Further purification by column chromatography on silica gel (eluting with 1:1 cyclohexane/ethyl acetate) gave 4.17 g (90%) of trans methanesulfonic acid 4-tert-butoxycarbonylamino-cyclohexylmethyl ester as a white solid. 1H NMR (400 MHz, CDCl3) δ: 4.37 (br s, 1H), 4.02 (d, 2H), 3.39 (br s, 1H), 3.00 (s, 3H), 2.11-2.00 (m, 2H), 1.91-1.81 (m, 2H), 1.77-1.64 (m, 1H), 1.43 (s, 9H), 1.18-1.05 (m, 4H).

Workup

  1. concentrationThe mixture was then concentrated under vacuum
  2. customThe residue was partitioned between ethyl acetate and water
  3. extractionthe aqueous phase was extracted with ethyl acetate (×2)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe residue was triturated with cyclohexane
  8. customthen dried under vacuum
  9. customto give a white solid
  10. customFurther purification by column chromatography on silica gel (eluting with 1:1 cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-0a4b0e87582645e99ab38067eb323412
Source dataset
uspto-grants-2013_06
Patent number
US08461328B2

Reaction notes

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