Water → Tert-butyl 3-(1-fluorocyclohexyl)-2-(4-methylphenylsulfonamido)propyl(methyl)carbamate

HRID 1254359Notes

Reaction equation

HRID 1254359 reaction equation
O[C:2]1([CH2:8][CH:9]([NH:20][S:21]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH2:10][N:11]([CH3:19])[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.CN(S(F)(F)[F:35])C.O>C(Cl)Cl>[F:35][C:2]1([CH2:8][CH:9]([NH:20][S:21]([C:24]2[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH2:10][N:11]([CH3:19])[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 962WaterHCID 123203Sulfur, trifluoro(N-methylmethanaminato)-HCID 59383054Tert-butyl 3-(1-hydroxycyclohexyl)-2-(4-methylphenylsulfonamido)-propyl(methyl)carbamate

Product 1

HCID 59382997Tert-butyl 3-(1-fluorocyclohexyl)-2-(4-methylphenylsulfonamido)propyl(methyl)carbamateYield 19.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 3-(1-hydroxycyclohexyl)-2-(4-methylphenylsulfonamido)-propyl(methyl)carbamate (9.23 g, 21 mmol) in dry CH2Cl2 (100 mL) at −78° C. was added (dimethylamino)sulfur trifluoride (4.2 g, 32 mmol). The reaction mixture was poured into water (80 mL) and extracted with CH2Cl2 (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica eluted with 10:90 hexanes/EtOAc to afford a light yellow solid. The crude product was purified further by preparative HPLC to give tert-butyl 3-(1-fluorocyclohexyl)-2-(4-methylphenylsulfonamido)propyl(methyl)carbamate (1.85 g). 1H NMR (400 MHz, CDCl3): 1.24-1.52 (m, 19H), 1.74-1.79 (m, 3H), 2.42 (s, 3H), 2.50 (s, 3H), 3.15 (m, 1H), 3.40 (m, 2H), 7.30 (d, 2H), 7.72 (d, J=8.4, 2H). MS (E/Z): 443 (M+H+).

Workup

  1. extractionextracted with CH2Cl2 (3×50 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography on silica
  6. washeluted with 10:90 hexanes/EtOAc
  7. customto afford a light yellow solid
  8. customThe crude product was purified further by preparative HPLC

Sources & evidence

ORD record
ord-c14ebae1807049b3a7ae978c627c0c61
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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