Methanesulfonyl chloride → HCID 86603411, compound

HRID 1028511Notes

Reaction equation

HRID 1028511 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[CH2:9][N:10]([CH2:21][C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=2[C:32]2[CH:37]=[C:36]([CH:38]([CH3:40])[CH3:39])[CH:35]=[CH:34][C:33]=2[O:41][CH3:42])[C:11](=[O:20])[O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.CS(Cl)(=O)=O.C([O-])(O)=O.[Na+].[N-:63]=[N+:64]=[N-:65].[Na+]>C(Cl)Cl.O>[N:63]([CH:8]([C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH2:9][N:10]([CH2:21][C:22]1[CH:27]=[C:26]([C:28]([F:30])([F:31])[F:29])[CH:25]=[CH:24][C:23]=1[C:32]1[CH:37]=[C:36]([CH:38]([CH3:40])[CH3:39])[CH:35]=[CH:34][C:33]=1[O:41][CH3:42])[C:11](=[O:20])[O:12][CH2:13][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)=[N+:64]=[N-:65]

Participants

8

Reactant 5

HCID 31297Methanesulfonyl chlorideHCID 33557Sodium AzideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 66716596HCID 66716596, compound

Product 1

HCID 86603411HCID 86603411, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of benzyl [2-(4-chlorophenyl)-2-hydroxyethyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate. (44 mg, 0.07 mmol) in CH2Cl2 (6 mL) was cooled to 0° C. and N,N diisopropylethylamine (63 lit, 0.36 mmol) was added followed by methanesulfonyl chloride (14 μL, 0.18 mmol). The reaction was stirred at 0° C. for 30 minutes and then poured into saturated NaHCO3 (15 mL). The resultant mixture was extracted with EtOAc (50 mL) and the organic layer was washed with brine (15 mL), dried over Na2SO4, filtered through a short plug of silica gel, and concentrated. The residue was redissolved in DMPU (6 mL) and sodium azide (12 mg, 0.18 mmol) was added. The reaction was stirred at room temperature for 24 hours and then poured into H2O (15 mL). The resultant mixture was extracted with EtOAc (50 mL) and the organic layer was washed with H2O (2×15 mL) and brine (15 mL), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 25% EtOAc/hexanes afforded benzyl [2-azido-2-(4-chlorophenyl)ethyl]{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}carbamate. Rf=0.66 (25% EtOAc/hexanes). LCMS=637.3 (M+1)+. 1H NMR (C6D6, 600 MHz, peaks doubled; rotamers and/or atropisomers present) δ 8.03-6.52 (m, 15 H), 5.00-5.08 (m, 2H), 4.76-4.12 (m, 3H), 3.28-2.86 (m, 5H), 2.77 (m, 1H), 1.23-1.18 (m, 6H).

Workup

  1. extractionThe resultant mixture was extracted with EtOAc (50 mL)
  2. washthe organic layer was washed with brine (15 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered through a short plug of silica gel
  5. concentrationconcentrated
  6. dissolutionThe residue was redissolved in DMPU (6 mL)
  7. stirringThe reaction was stirred at room temperature for 24 hours
  8. extractionThe resultant mixture was extracted with EtOAc (50 mL)
  9. washthe organic layer was washed with H2O (2×15 mL) and brine (15 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification of the residue by flash chromatography with 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-ada1dae0cab14d438a3dba1861b693be
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

Loading…