Sodium borohydride → 5-Bromo-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester

HRID 1807960Notes

Reaction equation

HRID 1807960 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([Br:27])=[CH:8][C:9]=1[N:10]([C:18]([CH:20]1[CH2:25][CH2:24][CH: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].[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([Br:27])=[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]([CH:20]1[CH2:21][CH2:22][CH:23]([CH3:26])[CH2:24][CH2:25]1)=[O:19])=[O:4]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 597523505-Bromo-3-[(4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 577953645-Bromo-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl esterYield 77%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

5-Bromo-3-[(4-methyl-cyclohexanecarbonyl)-(4-oxo-cyclohexyl)-amino]-thiophene-2-carboxylic acid methyl ester (473 mg, 1.04 mmol) was dissolved in methanol (10.4 ml), cooled to 0° C. and treated with sodium borohydride (43 mg, 1.14 mmol). After 30 minutes of stirring at 0° C., the reaction was left stirring at room temperature for 30 min and quenched with a 10% solution of hydrochloric acid (20 ml). The aqueous phase was extracted with ethyl acetate (3×10 mL) and the combined ethyl acetate layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel column chromatography using EtOAc:hexanes as eluent to furnished 5-Bromo-3-[(4-hydroxy-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (365 mg, 77% yield) as a solid. 1H NMR (CDCl3, 400 MHz): 6.82 (s, 1H), 4.56 (m, 1H), 3.82 (s, 3H), 3.45 (m, 1H), 2.08-1.72 (m, 4H), 1.75 (m, 1H), 1.68-1.23 (m, 11H), 0.98 (m, 1H), 0.80 (d, 3H), 0.68 (m, 2H).

Workup

  1. waitthe reaction was left
  2. stirringstirring at room temperature for 30 min
  3. customquenched with a 10% solution of hydrochloric acid (20 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×10 mL)
  5. dry with materialthe combined ethyl acetate layer was dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-a24beab7ac6044f1a223fc28a861b86f
Source dataset
uspto-grants-2013_01
Patent number
US08357718B2

Reaction notes

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