Boron tribromide → 1-Benzhydryl-3-[(4-hydroxyphenyl)(methylsulfonyl)methylene]azetidine

HRID 1058784Notes

Reaction equation

HRID 1058784 reaction equation
[CH:1]([N:14]1[CH2:17][C:16](=[C:18]([C:23]2[CH:28]=[CH:27][C:26]([O:29]C)=[CH:25][CH:24]=2)[S:19]([CH3:22])(=[O:21])=[O:20])[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br>ClCCl>[CH:1]([N:14]1[CH2:15][C:16](=[C:18]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)[S:19]([CH3:22])(=[O:21])=[O:20])[CH2:17]1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 225654111-Benzhydryl-3-[(4-methoxyphenyl)(methylsulfonyl)methylene]azetidine

Product 1

HCID 225654101-Benzhydryl-3-[(4-hydroxyphenyl)(methylsulfonyl)methylene]azetidineYield 44.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

On carrying out the operation according to the procedure of Example 32 starting with 1.4 g of 1-benzhydryl-3-[(4-methoxyphenyl)(methylsulfonyl)methylene]azetidine, 10 cm3 of a 1 M boron tribromide solution and 100 cm3 of dichloromethane, the residue obtained is purified by chromatography on a silica gel column (particle size 0.04-0.06 mm, diameter 3.5 cm, height 24 cm) at a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (50/50 by volume) as eluents and collecting 25 cm3 fractions. Fractions 21 to 37 are combined and concentrated to dryness under reduced pressure (2.7 kPa). The solid obtained is crystallized from a mixture of 30 cm3 of ethyl ether. 0.6 g of 1-benzhydryl-3-[(4-hydroxyphenyl)(methylsulfonyl)methylene]azetidine is obtained melting at 211° C. [NMR spectrum in DMSO-d6, T=300K, δ in ppm (300 MHz): 2.90 (3H, s, SCH3), 3.80 (2H, s, NCH2), 4.20 (2H, s, NCH2), 4.75 (1H, s, NCH), 6.80 (2H, d, J=7 Hz, 2CH arom.), between 7.10 and 7.35 (8H, m, 8CH arom.), 7.48 (4H, d, J=7 Hz, 4CH arom.), 9.80 (1H, s, OH)].

Workup

  1. customthe residue obtained
  2. customis purified by chromatography on a silica gel column (particle size 0.04-0.06 mm, diameter 3.5 cm, height 24 cm) at a nitrogen pressure of 0.5 bar with a mixture of cyclohexane and ethyl acetate (50/50 by volume) as eluents
  3. customcollecting 25 cm3 fractions
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. customThe solid obtained
  6. customis crystallized from a mixture of 30 cm3 of ethyl ether

Sources & evidence

ORD record
ord-1d1925cfb62142af874a7029787d6483
Source dataset
uspto-grants-2003_02
Patent number
US06518264B2

Reaction notes

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