1,2-Dimethoxyethane → tert-Butyl[1-(5-chloro-2-methoxy-4-methyl-3-vinylphenyl)ethyl]carbamate

HRID 511008Notes

Reaction equation

HRID 511008 reaction equation
Br[C:2]1[C:3]([O:20][CH3:21])=[C:4]([CH:10]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].CO[CH2:24][CH2:25]OC.C(=O)([O-])[O-].[K+].[K+].N1C=CC=CC=1.C(B1OB(C=C)OB(C=C)O1)=C>O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:15]([O:14][C:13](=[O:19])[NH:12][CH:10]([C:4]1[CH:5]=[C:6]([Cl:9])[C:7]([CH3:8])=[C:2]([CH:24]=[CH2:25])[C:3]=1[O:20][CH3:21])[CH3:11])([CH3:18])([CH3:17])[CH3:16]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 27348062,4,6-Trivinylboroxin-Pyridine ComplexHCID 88543336Tert-butyl[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]carbamate

Product 1

HCID 123890412tert-Butyl[1-(5-chloro-2-methoxy-4-methyl-3-vinylphenyl)ethyl]carbamateYield 100%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethyl]carbamate (80 mg, 0.20 mmol) (Example 113, Step 1; peak 2 from chiral separation) in water (0.44 mL) was added 1,2-dimethoxyethane (1.0 mL), potassium carbonate (29 mg, 0.21 mmol), pyridine:trivinylboroxin (1:1) (80 mg, 0.32 mmol) and tetrakis(triphenylphosphine)palladium(0) (11 mg, 0.0092 mmol). The resulting suspension was heated at 80° C. overnight. The reaction was diluted with water and EtOAc. The aqueous phase was extracted with EtOAc once. The combined organic solutions were washed with brine, dried over sodium sulfate and concentrated. The residue was purified on silica gel using 0-100% EtOAc in hexane to give the desired compound (68 mg, 100%). LCMS calculated for C12H14ClO (M−NHBoc)+: m/z=209.1. found: 209.0.

Workup

  1. extractionThe aqueous phase was extracted with EtOAc once
  2. washThe combined organic solutions were washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified on silica gel using 0-100% EtOAc in hexane

Sources & evidence

ORD record
ord-d3cc9227aebc43ec83bb3c5ba3a0aa5b
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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