1-Bromohexane → Benzoic Acid

HRID 1265241Notes

Reaction equation

HRID 1265241 reaction equation
C[O:2][C:3](=[O:27])[C:4]1[CH:9]=[CH:8][C:7](C(C2C(O)=CC3C(C)(C)CCC(C)(C)C=3C=2)=O)=[CH:6][CH:5]=1.[OH-].[K+].BrCCCCCC>CS(C)=O>[C:3]([OH:27])(=[O:2])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 81011-BromohexaneHCID 14797Potassium HydroxideHCID 10021814HCID 10021814, compound

Product 1

HCID 243Benzoic Acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

A solution of the 4-[(3-hydroxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid methyl ester (from Example 7, 433 mg, 1.18 mmol) in DMSO (2 mL) was treated with KOH (1.5 mmol) at 0° C. and allowed to warm to ambient temperature over 1 h. The yellow solution was cooled again to 0° C. and treated with a solution of bromohexane (156 mL, 1.30 mmol) in DMSO (1 mL) and allowed to warm to ambient temperature and stirred for 10 h. The reaction was quenched with saturated aqueous NH4Cl. The aqueous solution was adjusted to pH=3 with 1M HCl and extracted with EtOAc, 3×. The organic layers were combined and washed with water (2×) and brine. The organic solution was dried (NaSO4), filtered, and concentrated. Purification by silica gel radial chromatography (20:1=hexane:Et2O) gave 4-[2-hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid, 317 mg (62%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ8.14 (½ABq, J=8.4 Hz, 2H, ArH), 7.84 (½ABq, J=8.4 Hz, 2H, ArH), 7.47 (s, 1H, ArH), 6.81 (s, 1H, ArH), 3.80 (t, J=6.2 Hz, 2H, OCH2), 1.17 (m, 4H, 2CH2), 1.34 (m, 2H, CH2), 1.32 (s, 6H, 2CH3), 1.28 (s, 6H, 2CH3), 1.11 (m, 4H, 2CH2), 0.95 (m, 2H, CH2), 0.80 (t, J=7.1 Hz, 3H, CH3). The hexyloxyketo acid (87 mg, 0.19 mmol) in EtOH (2 mL) was converted into the oxime derivative as described in Example 4 to provide, after recrysallization (CH2Cl2/hexanes), 4-[(3-hexyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid oxime (114), 312 mg (60%) as a white solid: mp 197-199° C. (d); 1H NMR (400 MHz, CDCl3) δ8.14 (½ABq, J=8.5 Hz, 2H, ArH), 7.57 (½ABq, J=8.5 Hz, 2H, ArH), 7.22 (s, 1H, ArH), 6.85 (s, 1H, ArH), 3.82 (t, J=6.3 Hz, 2H, OCH2), 1.70 (m, 4H, 2CH2), 1.45 (m, 2H, CH2), 1.32 (s, 6H, 2CH3), 1.25 (s, 6H, 2CH3), 1.13 (m, 6H, 3CH2), 0.80 (t, J=6.8 Hz, 3H, CH3); 13C NMR (100 MHz, CDCl3) δ155.7, 153.8, 147.8, 141.1, 137.0, 130.3, 129.9, 128.4, 127.0, 118.5, 110.0, 68.3, 35.3, 35.0, 34.8, 33.8, 31.9, 31.8, 31.4, 29.0, 25.4, 22.5, 13.9.

Workup

  1. temperatureThe yellow solution was cooled again to 0° C.
  2. temperatureto warm to ambient temperature
  3. customThe reaction was quenched with saturated aqueous NH4Cl
  4. extractionextracted with EtOAc, 3×
  5. washwashed with water (2×) and brine
  6. dry with materialThe organic solution was dried (NaSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel radial chromatography (20:1=hexane:Et2O)

Sources & evidence

ORD record
ord-946b34807ca54209b5aa30a52cf840b1
Source dataset
uspto-grants-2003_04
Patent number
US06545049B1

Reaction notes

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