Benzene → 4-Chloro-2-(3-chloropropylamino)-6-methyl-10,10dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid methyl ester

HRID 1695288Notes

Reaction equation

HRID 1695288 reaction equation
[Na].[BH4-].[Cl:3]C(C)C(O)=O.[CH:9]1[CH:14]=CC=C[CH:10]=1.[CH3:15][O:16][C:17]([C:19]1[CH:20]=[C:21]([CH3:38])[C:22]2[O:28][C:27]3[C:29]([Cl:34])=[CH:30][C:31]([NH2:33])=[CH:32][C:26]=3[CH2:25][S:24](=[O:36])(=[O:35])[C:23]=2[CH:37]=1)=[O:18]>C1COCC1>[CH3:15][O:16][C:17]([C:19]1[CH:20]=[C:21]([CH3:38])[C:22]2[O:28][C:27]3[C:29]([Cl:34])=[CH:30][C:31]([NH:33][CH2:10][CH2:9][CH2:14][Cl:3])=[CH:32][C:26]=3[CH2:25][S:24](=[O:36])(=[O:35])[C:23]=2[CH:37]=1)=[O:18]

Participants

6

Reactant 4

HCID 241BenzeneHCID 117342-Chloropropionic acidHCID 115596902-Amino-4-chloro-6-methyl-10,10-dioxo-10,11-dihydro-5-oxa-10lambda *6*-thia-dibenzo[a,d]cycloheptene-8-carboxylic acid methyl esterHCID 131720715CID 131720715

Product 1

HCID 1317285294-Chloro-2-(3-chloropropylamino)-6-methyl-10,10dioxo-10,11-dihydro-5-oxa-10lambda*6*-thia-dibenzo[a,d]-cycloheptene-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Powdered sodium-borohydride (0.93 g, 24 mmol) was added in portions at 0° C., to a solution of chloropropionic acid (5.32 g, 49 mmol) in THF (13 mL), and benzene (210 mL). Reaction mixture was warmed to room temperature and stirred for 1 h, and compound of Example 1 (3.0 g, 8.17 mmol) was added. Reaction mixture was refluxed for 3 h. Reaction mixture was cooled and quenched using sodium bicarbonate solution, and extracted with ethylacetate. Organic layer was washed with water (100 mL) and brine (50 mL). The crude product obtained was purified by column chromatography (silica gel, ethylacetate/pet. ether) to obtain the title compound. Yield: 3.7 g (99%); 1H NMR (DMSO-d6, 300 MHz): δ 1.96 (q, 2H, CH2), 2.62 (s, 3H, CH3), 3.11 (q, 2H, CH2), 3.72 (t, 2H, CH2), 3.85 (s, 3H, OCH3), 5.12 (s, 2H, CH2), 6.29 (s, 1H, Ar), 6.31 (s, 1H, Ar), 8.07 (s, 1H, Ar), 8.13 (s, 1H, Ar); MS: m/e (El) 443 (M+).

Workup

  1. customReaction mixture
  2. customReaction mixture
  3. temperaturewas refluxed for 3 h
  4. customReaction mixture
  5. temperaturewas cooled
  6. customquenched
  7. extractionextracted with ethylacetate
  8. washOrganic layer was washed with water (100 mL) and brine (50 mL)
  9. customThe crude product obtained
  10. customwas purified by column chromatography (silica gel, ethylacetate/pet. ether)

Sources & evidence

ORD record
ord-ea83bf9e38b2404899550e3789ed9fb3
Source dataset
uspto-grants-2012_04
Patent number
US08163730B2

Reaction notes

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