Triethylamine → (+/-)-trans-1,2,4,5-Tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid

HRID 618460Notes

Reaction equation

HRID 618460 reaction equation
[CH3:1][CH:2]1[S:8][CH:7]([C:9]([OH:11])=[O:10])[CH2:6][C:5]2[CH:12]=[C:13]3[O:18][CH2:17][O:16][C:14]3=[CH:15][C:4]=2[C:3]1=[O:19].C(N(CC)CC)C.C[C@H](N)[C@H](O)C1C=CC=CC=1>CO.O>[CH3:1][C@@H:2]1[S:8][C@@H:7]([C:9]([OH:11])=[O:10])[CH2:6][C:5]2[CH:12]=[C:13]3[O:18][CH2:17][O:16][C:14]3=[CH:15][C:4]=2[C:3]1=[O:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10297PhenylpropanolamineHCID 159224451,2,4,5-Tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid

Product 1

HCID 9845635(+/-)-trans-1,2,4,5-Tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
50 °C

Procedure

In 500 mL of methanol-water (volume ratio 1:1) was suspended 50.6 g of a racemic mixture, 1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid (content 98.8%; trans compound 90.2%, cis compound 9.6%). To the suspension was added 25 mL of triethylamine, which was made into a solution by heating (50° C.). To the solution was added 13.6 g (0.5 equivalent) of (1R,2S)-norephedrine. The mixture was once made into a solution, which was crystallized in about 10 minutes, followed by cooling to 30° C. over about 60 minutes, and then to 5° C. The crystals were aged for 60 minutes at the same temperature. The resulting crystals were collected by filtration, washed with 200 mL of cold methanol-water (volume ratio 1:1) and dried at 35° C. under reduced pressure to afford 29.9 g of substantially pure (2R,4S)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid.(1R,2S)-norephedrine salt as colorless crystals [HPLC area percentage: (2R,4R):(2S,4S):(2S,4R):(2R,4S)=0.86%:0.46%:0.50%:97.9%].

Workup

  1. customwas crystallized in about 10 minutes
  2. temperatureby cooling to 30° C. over about 60 minutes
  3. customto 5° C
  4. filtrationThe resulting crystals were collected by filtration
  5. washwashed with 200 mL of cold methanol-water (volume ratio 1:1)
  6. customdried at 35° C. under reduced pressure

Sources & evidence

ORD record
ord-f2775e1a29c049ff803bf5481e72a248
Source dataset
uspto-grants-1999_09
Patent number
US05952512

Reaction notes

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