Benzyl Bromide → Methyl Benzoate

HRID 1265242Notes

Reaction equation

HRID 1265242 reaction equation
[CH3:1][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.[H-].[Na+].C(Br)C1C=CC=CC=1>CN(C=O)C>[CH3:1][O:2][C:3](=[O:27])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 10021814HCID 10021814, compound

Product 1

HCID 7150Methyl BenzoateYield 273.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

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 (237 mg, 0.65 mmol) in DMF (1mL) was treated with NaH (0.68 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 benzyl bromide (142 mg, 0.83 mmol) in DMF and allowed to warm to ambient temperature and stirred for 10 h. The reaction was quenched with saturated aqueous NH4Cl. The aqueous solution was 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 to give a colorless oil. Purification by silica gel flash chromatorgraphy (20:1=hexanes:EtOAc) gave 4-[3-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbonyl]benzoic acid methyl ester 242 mg (82%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ8.19 (½ABq, J=8.4 Hz, 2H, ArH), 7.81 (½ABq, J=8.4 Hz, 2H, ArH), 7.44 (s, 1H, ArH), 7.38 (m, 3H, ArH), 7.17 (m, 2H, ArH), 6.92 (s, 1H, ArH), 4.93 (s, 2H, OCH2), 3.95 (s, 3H, OCH3), 1.67 (m, 4H, 2CH2), 1.29 (s, 6H, 2CH3), 1.26(s, 6H, 2CH3). The benzyloxy keto ester (204 mg, 0.46 mmol) in MeOH (2 mL) was treated with hydroxylamine hydrochloride (97 mg, 1.4 mmol) and KOH (156 mg, 2.8 mmol), and the mixture was heated at reflux for 3 h. After 6 h, the mixture was cooled to room temperature and the ethanol was removed in vacuo. The residue was taken-up in water and the aqueous layer was adjusted to pH=4-5 with 1 M aqueous HCl. The aqueous solution was extracted with EtOAc, 3×. The organic layers were combined and washed with water (2×) and brine. The organic solution was dried (Na2SO4), filtered, and concentrated to give a white foamy solid. Recrystallization (THF/hexanes) gave cis-4-[(3-benzyloxy-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) carbonyl]benzoic acid oxime (117) 186 mg (88%) as a white solid: mp 199-205° C. (d); IR (neat) 3500-3100 (br) m, 2963 s, 2934 s, 1694 s, 1613 w, 1505 w, 1321 m, 1265 m, 1024 w cm−1; 1H NMR (400 MHz, CDCl3) δ8.00 (½ABq, J=8.4 Hz, 2H, ArH), 7.56 (½ABq, J=8.4 Hz, 2H, ArH), 7.20 (m, 3H, ArH), 7.15 (s, 1H, ArH), 7.08 (m, 2H, ArH), 6.91 (s, 1H, ArH), 4.96 (s, 2H, OCH2), 1.69 (m, 4H, 2CH2), 1.27 (s, 6H, 2CH3), 1.24 (s, 6H, 2CH3); HRMS (EI−, 70 ev) calcd. for C29H31NO4: 457.2253, found 457.2226; anal. calcd. for C29H31NO4; C176.12; H1 6.83; N1 3.06, found C1 75.83; H1 6.95; N1 2.90.

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. extractionThe aqueous solution was extracted with EtOAc, 3×
  5. washwashed with water (2×) and brine
  6. dry with materialThe organic solution was dried (NaSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a colorless oil
  10. customPurification by silica gel flash chromatorgraphy (20:1=hexanes:EtOAc)

Sources & evidence

ORD record
ord-e7f996d9ac6e4edca12b1a6faebe6a2e
Source dataset
uspto-grants-2003_04
Patent number
US06545049B1

Reaction notes

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