Hydrochloric Acid → 5-(4-Chlorobenzyl)-8-hydroxy-4-(2-hydroxyethyl)-2-methyl-3,5-dihydro-2H-thiopyrano[4,3,2-cd]indole

HRID 1034261Notes

Reaction equation

[H-].[Na+].CC(S)(C)C.[Cl:8][C:9]1[CH:33]=[CH:32][C:12]([CH2:13][N:14]2[C:22]3[CH:21]=[CH:20][C:19]([O:23]C)=[C:18]4[S:25][CH:26]([CH3:28])[CH2:27][C:16]([C:17]=34)=[C:15]2[CH2:29][CH2:30][OH:31])=[CH:11][CH:10]=1.Cl>CN(C=O)C.CN1C(=O)N(C)CCC1.O>[Cl:8][C:9]1[CH:33]=[CH:32][C:12]([CH2:13][N:14]2[C:22]3[CH:21]=[CH:20][C:19]([OH:23])=[C:18]4[S:25][CH:26]([CH3:28])[CH2:27][C:16]([C:17]=34)=[C:15]2[CH2:29][CH2:30][OH:31])=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a suspension of 97% NaH (120 mg, 4.88 mmol) in DMF (10 mL) and DMPU (1 mL) cooled to 0° C., there was added 2-methyl-2-propanethiol (550 mg, 6.10 mmol) and the resulting mixture was stirred at 0° C. for one hour. To this clear solution there was added a solution of product from Step 4 (490 mg, 1.22 mmol) in DMF (4 mL). The mixture was heated at 140° C. for 19 hours, cooled, diluted with H2O, acidified with 1N HCl and extracted 3× with Et2O. These extracts were washed 2× with brine, dried, and evaporated. The residue was chromatographed on silica gel, eluting with a 1:1 mixture of EtOAc and hexane, to afford the title product as a thick oil.

Workup

temperatureThe mixture was heated at 140° C. for 19 hours
temperaturecooled
extractionextracted 3× with Et2O
washThese extracts were washed 2× with brine
customdried
customevaporated
customThe residue was chromatographed on silica gel
washeluting with a 1:1 mixture of EtOAc and hexane

Sources & evidence

ORD record: ord-1545c4b736c846e4abcabaa0b2a8cb18
Source dataset: uspto-grants-1994_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05314898

Reaction notes

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