Diisopropylethylamine → 2-Chloro-4-[[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]-6-methylphenol

HRID 393028Notes

Reaction equation

HRID 393028 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([CH3:12])[C:10]=1[OH:11])[C:5]([OH:7])=O.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH3:49][C:50]([Si:53]([CH3:64])([CH3:63])[O:54][C:55]1[CH:56]=[C:57]([CH2:61][NH2:62])[CH:58]=[CH:59][CH:60]=1)([CH3:52])[CH3:51]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]([NH:62][CH2:61][C:57]2[CH:58]=[CH:59][CH:60]=[C:55]([O:54][Si:53]([C:50]([CH3:52])([CH3:51])[CH3:49])([CH3:63])[CH3:64])[CH:56]=2)=[O:7])[CH:8]=[C:9]([CH3:12])[C:10]=1[OH:11]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 222661693-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]benzenemethanamineHCID 226613313-Chloro-4-hydroxy-5-methylbenzoic acid

Product 1

HCID 226612862-Chloro-4-[[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]-6-methylphenolYield 59%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A suspension of 3-chloro-4-hydroxy-5-methylbenzoic acid (4.7 g, 25.2 mmol) in dichloromethane (50 mL) was cooled to 0° C. and BOP reagent (12.3 g, 27.8 mmol) was added, followed by diisopropylethylamine (13.2 mL, 75.6 mmol). A solution of 3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]benzenemethanamine (Example 8; 6.59 g, 27.8 mmol) in dry dichloromethane (10 mL) was added by syringe and the resulting solution was stirred at ˜0° C. for 3 h. The solvent was evaporated and ethyl acetate (200 mL) was added. The solution was washed with 1 M HCl (2×50 mL), aqueous sodium hydrogen carbonate (100 mL), brine (100 mL), and water (100 mL)dried (MgSO4), filtered, evaporated, and chromatographed (30% ethyl acetate/hexanes) to give 2-chloro-4-[[[[3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]phenyl]methyl]amino]carbonyl]-6-methylphenol (6.03 g, 59%) as a pale pink solid.

Workup

  1. customThe solvent was evaporated
  2. additionethyl acetate (200 mL) was added
  3. washThe solution was washed with 1 M HCl (2×50 mL), aqueous sodium hydrogen carbonate (100 mL), brine (100 mL), and water (100 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customchromatographed (30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-c47d161447864d8c89a010a89fff4f23
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

Loading…