Tert-butyl 4-(bromomethyl)benzoate → HCID 67211831, compound

HRID 1401884Notes

Reaction equation

HRID 1401884 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH2:17][CH2:16][C@@H:15]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH:13]=2)=[CH:8][CH:7]=1)[CH3:2].C[Si](C)(C)N[Si](C)(C)C.[Li].[C:33]([O:37][C:38](=[O:47])[C:39]1[CH:44]=[CH:43][C:42]([CH2:45]Br)=[CH:41][CH:40]=1)([CH3:36])([CH3:35])[CH3:34]>C1COCC1>[C:33]([O:37][C:38](=[O:47])[C:39]1[CH:40]=[CH:41][C:42]([CH2:45][CH:5]([C:6]2[CH:7]=[CH:8][C:9]([C:12]3[CH2:17][CH2:16][C@@H:15]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH:13]=3)=[CH:10][CH:11]=2)[C:4]([O:3][CH2:1][CH3:2])=[O:22])=[CH:43][CH:44]=1)([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 11414578Tert-butyl 4-(bromomethyl)benzoateHCID 57426343Lithium bis(trimethylsilyl)amideHCID 67211343HCID 67211343, compound

Product 1

HCID 67211831HCID 67211831, compoundYield 40.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To [4-((R)-4-tert-Butyl-cyclohex-1-enyl)-phenyl]-acetic acid ethyl ester (95 mg. 0.32 mmol) in anhydrous THF (5 mL), chilled to −78° C. was added 380 uL (0.38 mmol) of 1M lithium hexamethyldisilazane in THF. The resulting solution was stirred for 1 hr before 4-Bromomethylbenzoic acid tert-butyl ester (94 mg, 0.35 mmol) was added. The reaction mixture was allowed to warm to rt overnight then quenched with saturated NH4Cl solution. After partitioning between ethyl acetate and brine the organic portion was dried over Na2SO4 and concentrated under reduced pressure. Purification of the crude by prep TLC (Analtech, 2 mm silica plates) using an hexane/ethyl acetate (10:1) gave 63 mg of product. 1H NMR (500 MHz, CDCl3): 7.83 (d, J=8.5 Hz, 2 H), 7.31 (d, J=8.5 Hz, 2 H), 7.20 (d, J=8 Hz, 2 H), 7.14 (d, J=8 Hz, 2 H), 6.12 (m, 1H), 4.03 (q, J=7 Hz 2 H), 3.80 (t, J=8.5 Hz, 1H), 3.41 (dd, =14, 8.5 Hz, 1 H), 3.03 (dd, J=14, 7 Hz, 1 H), 2.56-2.4 (m, 2H), 2.35-2.2 (m, 1H). 2.05-1.9 (m, 2H), 1.56 (s, 9 H), 1.36-1.2 (m, 2 H), 1.11 (t, J=7 Hz, 3 H), 0.89 (s, 9H).

Workup

  1. additionwas added
  2. customthen quenched with saturated NH4Cl solution
  3. customAfter partitioning between ethyl acetate and brine the organic portion
  4. dry with materialwas dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the crude by prep TLC (Analtech, 2 mm silica plates)

Sources & evidence

ORD record
ord-846cdd41bc37480c8b0db3e67a3780da
Source dataset
uspto-grants-2014_12
Patent number
US08907103B2

Reaction notes

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