Pentane → (4-Fluoro-2-(2-methyl-allyl)-phenyl]-carbamic acid tert-butyl ester

HRID 2249935Notes

Reaction equation

HRID 2249935 reaction equation
[C:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Li][C:17]([CH3:20])([CH3:19])[CH3:18].CCCCC.C(Br)C(=C)C>C1COCC1>[C:4]([O:3][C:1](=[O:2])[NH:8][C:9]1[CH:14]=[CH:13][C:12]([F:15])=[CH:11][C:10]=1[CH2:19][C:17]([CH3:20])=[CH2:18])([CH3:7])([CH3:6])[CH3:5]

Participants

6

Reactant 4

HCID 8003PentaneHCID 3577853-Bromo-2-methyl-1-propeneHCID 4935450Tert-butyl 4-fluorophenylcarbamateHCID 178418306HCID 178418306, compound

Product 1

HCID 68684743(4-Fluoro-2-(2-methyl-allyl)-phenyl]-carbamic acid tert-butyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

A solution of N-Boc-4-fluoroaniline (9.02 g, 42.7 mmol) in THF (112 mL) was cooled to −60° C. using a cryocool instrument. The solution was treated with 1.7 M t-BuLi in pentane (63 mL, 106.7 mmol) dropwise. After the first equivalent of base was consumed, a yellow solution formed. The reaction was allowed to warm to −20° C. and was stirred at that temperature for 2.5 hours. The reaction was then treated with a solution of methallyl bromide (5.67 g, 42.7 mmol) in THF (35 mL) dropwise and stirred for an additional 1.5 hours at −20° C. The reaction was then quenched by addition of water. After coming to room temperature, the reaction was treated with ethyl acetate and extracted with water and brine, dried over MgSO4 and filtered. The solvent was then removed and the residue was purified on silica gel using a gradient of 0-25% ethyl acetate in hexane to afford 11.3 g (80% yield) of [4-Fluoro-2-(2-methyl-allyl)-phenyl]-carbamic acid tert-butyl ester as a white solid; 1H NMR (CDCl3, 400 MHz) δ 1.50 (s, 9H), 1.72 (s, 3H), 3.28 (s, 2H), 4.71 (s, 1H), 4.92 (s, 1H), 6.32-6.50 (m, 1H), 6.86 (dd, 1H, J1, =3.0, J2=9.1), 6.93 (ddd, 1H, J1, =3.0, J2=8.5, J3=11.5), 7.65-7.82 (m, 1H); HPLC-MS calcd. for C15H20FNO2 (M+H+-tBu) 210.1. found 210.3.

Workup

  1. customAfter the first equivalent of base was consumed
  2. customa yellow solution formed
  3. stirringstirred for an additional 1.5 hours at −20° C
  4. customThe reaction was then quenched by addition of water
  5. customAfter coming to room temperature
  6. additionthe reaction was treated with ethyl acetate
  7. extractionextracted with water and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customThe solvent was then removed
  11. customthe residue was purified on silica gel using a gradient of 0-25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-5b2338a8f67a46debcb7ff74a79941b7
Source dataset
uspto-grants-2008_01
Patent number
US07314872B2

Reaction notes

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