Hydrochloric Acid → HCID 178499333, compound

HRID 244900Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]#[C:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:8][C:9]=1[N:10]([C:18]([C@H:20]1[CH2:25][CH2:24][C@H:23]([CH3:26])[CH2:22][CH2:21]1)=[O:19])[CH:11]1[CH2:16][CH2:15][C:14](=[O:17])[CH2:13][CH2:12]1)=[O:4].O.[BH4-].[Na+].Cl>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]#[C:28][C:29]([CH3:30])([CH3:32])[CH3:31])=[CH:8][C:9]=1[N:10]([CH:11]1[CH2:12][CH2:13][CH:14]([OH:17])[CH2:15][CH2:16]1)[C:18]([C@H:20]1[CH2:25][CH2:24][C@H:23]([CH3:26])[CH2:22][CH2:21]1)=[O:19])=[O:4]

Participants

Conditions

Temperature: -25 °C

Procedure

5-(3,3-Dimethyl-but-1-ynyl)-3-[(trans-4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester (1 eq.) is dissolved in THF. Water is added to the reaction mixture and cooled to −25° C. NaBH4 (0.5 eq.) is added portion wise maintaining the temperature below −20° C. The mixture is stirred for 2 h at −25° C., 2N HCl is then added and the solution is warmed to room temperature. The phases are separated and the aqueous layer is washed with EtOAC. The organic phases are combined and washed with brine and dried over Na2SO4 and concentrated to dryness to give 5-(3,3-dimethyl-but-1-ynyl)-3-[(4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester as a 93:7 mixture of isomers. The crude cis/trans mixture is recrystallized in methanol to obtain >99% the trans isomer.

Workup

temperaturewise maintaining the temperature below −20° C
temperaturethe solution is warmed to room temperature
customThe phases are separated
washthe aqueous layer is washed with EtOAC
washwashed with brine
dry with materialdried over Na2SO4
concentrationconcentrated to dryness

Sources & evidence

ORD record: ord-5098ea3743ef4f83b27460da5acdf8ee
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658674B2

Reaction notes

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