Sodium triacetoxyborohydride → 3-(3-Benzyloxy-cyclobutylamino)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

HRID 1046403Notes

Reaction equation

HRID 1046403 reaction equation
Cl.[CH3:2][O:3][C:4]([C:6]1[S:7][C:8]([C:12]#[C:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:9][C:10]=1[NH2:11])=[O:5].[CH2:18]([O:25][CH:26]1[CH2:29][C:28](=O)[CH2:27]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(OCC)(=O)C>[CH3:2][O:3][C:4]([C:6]1[S:7][C:8]([C:12]#[C:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:9][C:10]=1[NH:11][CH:28]1[CH2:29][CH:26]([O:25][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:27]1)=[O:5]

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 149327873-(Benzyloxy)cyclobutan-1-oneHCID 1317307523-Amino-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester, hydrochloride salt

Product 1

HCID 581139753-(3-Benzyloxy-cyclobutylamino)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl esterYield 115.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-amino-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester, hydrochloride salt (750 mg, 2.74 mmol) and 3-benzyloxy-cyclobutanone (2.5 g, 14.3 mmol) in DCM (40 mL) was treated with sodium triacetoxyborohydride (3.34 g, 15.8 mmol) portionwise. The mixture was stirred at room temperature for 3 hours. The solution was diluted with ethyl acetate, washed sequentially with saturated aqueous sodium bicarbonate, water, and brine. The organic phase was dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (0-10% ethyl acetate:hexanes). This resulted in 1.26 g (quant. yield) of 3-(3-benzyloxy-cyclobutylamino)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester as a mixture of cis- and trans-isomers.

Workup

  1. washwashed sequentially with saturated aqueous sodium bicarbonate, water, and brine
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by silica gel chromatography (0-10% ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-ff2ae32a7af6467bb2d3bd1cb7f67624
Source dataset
uspto-grants-2013_10
Patent number
US08569302B2

Reaction notes

Loading…