Water → (2S,4R)-(+)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid

HRID 987405Notes

Reaction equation

HRID 987405 reaction equation
Cl.C(N=C=NCCCN(C)C)C.[CH3:13][C@@H:14]1[S:20][C@@H:19]([C:21]([OH:23])=[O:22])[CH2:18][C:17]2[CH:24]=[C:25]3[O:30][CH2:29][O:28][C:26]3=[CH:27][C:16]=2[C:15]1=[O:31].C(OC)(=O)[C@H](C1C=CC=CC=1)O.O>ClCCl.CN(C)C=O.CN(C)C1C=CN=CC=1>[CH3:13][C@H:14]1[S:20][C@H:19]([C:21]([OH:23])=[O:22])[CH2:18][C:17]2[CH:24]=[C:25]3[O:30][CH2:29][O:28][C:26]3=[CH:27][C:16]=2[C:15]1=[O:31]

Participants

8

Reactant 4

HCID 962WaterHCID 643570methyl (2S)-2-hydroxy-2-phenylacetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9845635(+/-)-trans-1,2,4,5-Tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid

Product 1

HCID 10802686(2S,4R)-(+)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acidYield 29.8%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (12.5 g) in dichloromethane (200 ml) was added to a solution of (±)-trans-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid (15.34 g) and methyl (S)-(+)-mandelate (18.19 g) in N,N-dimethylformamide (DMF) (200 ml) at 0° C., followed by the addition of 4-dimethylaminopyridine (DMAP) (3.34 g). This mixture was stirred at 0° C. for 1 hour and at room temperature for 15 hours, after which it was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried (MgSO4), after which the solvent was distilled off; the residual crystals were collected by filtration and washed with ether-hexane, followed by recrystallization twice from ethyl acetate-hexane to yield (S)-α-methoxycarbonylbenzyl ester of (2S,4R)-(+)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxylic acid (4.57 g, 19%). Colorless needles. Melting point 141-142° C. Optical rotation [a]D (23° C.) +239.7° (c=0.50, CHCl3).

Workup

  1. extractionextracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with water
  3. dry with materialdried (MgSO4)
  4. distillationafter which the solvent was distilled off
  5. filtrationthe residual crystals were collected by filtration
  6. washwashed with ether-hexane
  7. customfollowed by recrystallization twice from ethyl acetate-hexane

Sources & evidence

ORD record
ord-426dc726bb1b475cb70da79ed7ba843e
Source dataset
uspto-grants-2003_10
Patent number
US06632807B1

Reaction notes

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