2-Methylbenzenesulfonic acid → HCID 59201483, compound

HRID 2355328Notes

Reaction equation

HRID 2355328 reaction equation
[F:1][C:2]1([F:30])[CH2:7][CH2:6][CH:5]([CH2:8][C@H:9]([NH:22]C(=O)OC(C)(C)C)[CH2:10][N:11]([CH3:21])[C:12]([O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])=[O:13])[CH2:4][CH2:3]1.C1(C)C(S(O)(=O)=O)=CC=CC=1>CCOCC.CCO>[NH2:22][C@@H:9]([CH2:8][CH:5]1[CH2:4][CH2:3][C:2]([F:30])([F:1])[CH2:7][CH2:6]1)[CH2:10][N:11]([CH3:21])[C:12](=[O:13])[O:14][CH2:15][CH2:16][Si:17]([CH3:19])([CH3:20])[CH3:18]

Participants

5

Reactant 2

HCID 69252-Methylbenzenesulfonic acidHCID 67190056HCID 67190056, compound

Product 1

HCID 59201483HCID 59201483, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

(S)-tert-Butyl 1-(4,4-difluorocyclohexyl)-3-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-ylcarbamate (6.25 g, 0.0139 mol) was dissolved in a minimal volume of ether (100 mL) and added to a solution of toluenesulfonic acid (2.71 g, 0.0142 mol) in absolute EtOH (20 mL). This solution was placed on a rotary evaporator and the Et2O was removed at ambient temp. The flask was then lowered into the water bath (temperature: 60° C.) and the selective removal of the Boc group proceeded concurrently with removal of the remainder of solvent. The reaction was completed by 2 h and gave a white solid, which was washed with hexanes:EtOAc (5:1, v/v, 3×10 mL), basified with 1N NaOH (pH>10), and extracted with Et2O (3×50 mL) The combined Et2O extracts were washed with 1N aq NaOH (3×5 mL), brine (3×5 mL), dried, decanted and stripped to give the free base (S)-2-(trimethylsilyl)ethyl 2-amino-3-(4,4-difluorocyclohexyl)propyl(methyl)carbamate (3.68 g, 76%). 1H NMR (400 MHz, CD3OD): 4.17 (t, J=8.4 Hz, 2H), 3.15 (m, 1H), 2.93 (s, 3H), 2.61 (dd, J=12.0 & 4.0 Hz, 1H), 2.36 (dd, J=12.0 & 8.4 Hz, 1H), 2.12-1.16 (m, 11H), 1.00 (t, J=8.4 Hz, 2H), 0.04 (s, 9H); MS (E/Z): 351 (M+H+).

Workup

  1. customThis solution was placed on a rotary evaporator
  2. customthe Et2O was removed at ambient temp
  3. customwas then lowered into the water bath (temperature: 60° C.)
  4. customthe selective removal of the Boc group
  5. customproceeded concurrently with removal of the remainder of solvent
  6. customgave a white solid, which
  7. washwas washed with hexanes:EtOAc (5:1, v/v, 3×10 mL)
  8. extractionextracted with Et2O (3×50 mL) The combined Et2O extracts
  9. washwere washed with 1N aq NaOH (3×5 mL), brine (3×5 mL)
  10. customdried
  11. customdecanted

Sources & evidence

ORD record
ord-91f17d7a9f6044d09f0c4e46816bf95f
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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