Hydrogen Bromide → HCID 178478116, compound

HRID 1653837Notes

Reaction equation

HRID 1653837 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([CH2:14]O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[BrH:16].S(=O)(=O)(O)O.O>CCCCCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:13][CH2:12][C@H:11]([CH2:14][Br:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 260Hydrogen BromideHCID 962WaterHCID 1118Sulfuric AcidHCID 178520921HCID 178520921, compound

Product 1

HCID 178478116HCID 178478116, compoundYield 83.8%

Reagents, catalysts & solvents 1

HCID 8058HexaneSolvent

Procedure

To a stirred suspension of trans-(4-(4-chlorophenyl)cyclohexane)carboxylic acid (47.74 g) in dry ether (250 ml), under nitrogen, was added dropwise borane-methyl sulphide complex (8 ml; ca.10M solution--Aldrich). After 30 min the mixture was heated to reflux and further borane-methyl sulphide complex (16 ml) added. After 1 hr the mixture was cooled to room temperature and poured into methanol (500 ml). The solvent was evaporated in vacuo and the residue treated again with methanol (100 ml) followed by concentration in vacuo, to give trans-(4-(4-chlorophenyl)cyclohexyl) methanol (44 g), m.p. 60°-63°. A portion of this alcohol (41 g) was added to 48% hydrobromic acid (61 g) and conc. sulphuric acid (20 g). The mixture was stirred and heated at 140° for 5.5 hr, cooled and poured into iced water. The precipitate was filtered, dissolved in ether, washed with satd. aq. sodium bicarbonate and brine, dried over magnesium sulphate and the solvent evaporated in vacuo to leave a brown oil. Trituration with cold hexane gave trans-(4-(4-chlorophenyl)cyclohexyl)methyl bromide (44 g), m.p. 36°-38°. To magnesium turnings (33.06 g) in dry ether (70 ml) under nitrogen was added a crystal of iodine followed by a solution of the bromide (19.7 g) in ether (20 ml). The mixture was heated at reflux for a further 30 min, cooled to room temperature and then added dropwise to vigorously stirred acetic anhydride in dry ether (70 ml) at -78°, such that the temperature did not exceed -70°. The mixture was stirred at -78° for a further 1 hr, then allowed to warm to 0° and poured into satd. aq. ammonium chloride (200 ml). The mixture was stirred for 30 min then the organic phase was separated and washed with satd. aq. sodium bicarbonate and brine, dried over magnesium sulphate and concentrated in vacuo, to leave a white solid , which was recrystallised from hexane to afford the title compound (9.3 g), m.p. 58°-60°, NMR δH (CDCl3) 7.3-7.0 (4H, m), 2.55-2.3 (1H, m), 2.4-2.3 (2H, m), 2.15 (3H, s), 2-1.75 (5H, m), 1.6-1.45 (2H, m), 1.25-1.0 (2H, m).

Workup

  1. temperatureheated at 140° for 5.5 hr
  2. temperaturecooled
  3. filtrationThe precipitate was filtered
  4. dissolutiondissolved in ether
  5. washwashed with satd
  6. dry with materialaq. sodium bicarbonate and brine, dried over magnesium sulphate
  7. customthe solvent evaporated in vacuo
  8. customto leave a brown oil

Sources & evidence

ORD record
ord-dbd3888513884486be8bc1933bde8d9c
Source dataset
uspto-grants-1995_04
Patent number
US05403934

Reaction notes

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