Nadh → 1-(2-Chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-ol

HRID 58507

反応式

HRID 58507 の反応式
[Mg+2].[Cl-].[Cl-].[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11](=[O:18])[CH2:12][N:13]1[N:17]=[N:16][CH:15]=[N:14]1.C1N=C(N)C2N=CN([C@@H]3O[C@H](COP(OP(OC[C@H]4O[C@@H](N5C=C(C(N)=O)CC=C5)[C@H](O)[C@@H]4O)(O)=O)(O)=O)[C@@H](O)[C@H]3O)C=2N=1.ClC1C=CC=CC=1[C@@H](O)CN1N=NC=N1>C(OCC)(=O)C.C(OCCCC)(=O)C.CC(O)C.OCC(CO)O>[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH:11]([OH:18])[CH2:12][N:13]1[N:17]=[N:16][CH:15]=[N:14]1

参加物

9

反応物 4

HCID 439153NadhHCID 5360315Magnesium ChlorideHCID 67120090alpha-(2-Chlorophenyl)-2H-tetrazole-2-ethanol, (alphaR)-HCID 671200911-(2-Chlorophenyl)-2-(2H-tetrazol-2-yl)ethanone

生成物 1

HCID 671200881-(2-Chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-ol収率 99.6%

試薬・触媒・溶媒 4

HCID 753Glycerol溶媒HCID 3776Isopropanol溶媒HCID 8857Ethyl Acetate溶媒HCID 31272Butyl Acetate溶媒

実験手順

50 ml of the enzyme solution 2 containing the oxidoreductase SEQ NO: 2 were added to a mixture of 250 ml of a buffer (100 mM TEA, pH 8, 1 mM MgCl2, 10% glycerol), 50 g (225 mmol) of 1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-one (2N ketone), 4 mg NAD, 300 ml of 2-propanol and 150 mL of butyl acetate. The reaction mixture was stirred at room temperature. After 48 hours more than 98% of 2N ketone was reduced to corresponding (R)-1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-ol (R-2N alcohol) with >99% ee values. To this resulting mixture, 500 mL of ethyl acetate was added. After being separated, the organic layer thus formed was washed with 10% brine (3×500 mL). The organic layer thus formed was dried over magnesium sulfate and filtered and the filtrate was distilled under reduced pressure to give 50.4 g (224 mmol) of 1-(2-chlorophenyl)-2-(1,2,3,4-tetrazol-2-yl)ethan-1-ol (R-2N alcohol, optical purity 99.9%) as an oily residue. To this resulting crude product, 450 mL of tetrahydrofuran was added. After cooling to −15° C., 38 g (267 mmol) of chlorosulfonyl isocyanate was slowly added and stirred at −10° C. for 2 h. The slow addition of water induced termination of the reaction. The resulting solution was concentrated under reduced pressure until about 300 mL of the solvent was removed. The concentrate was diluted with 600 mL of ethyl acetate and washed with 10% brine (3×500 mL). The organic layer was concentrated under reduced pressure and the concentrate was dissolved in isopropanol (90 mL) to which heptane (180 mL) was slowly added, leading to the completion of crystallization. The precipitate thus obtained was filtered and washed to afford 51.8 g (194 mmol) of carbamic acid (R)-1-(2-chiorophenyl)-2-(tetrazol-2-yl)ethyl ester (optical purity 99.9%).

後処理

  1. customAfter being separated
  2. customthe organic layer thus formed
  3. washwas washed with 10% brine (3×500 mL)
  4. customThe organic layer thus formed
  5. dry with materialwas dried over magnesium sulfate
  6. filtrationfiltered
  7. distillationthe filtrate was distilled under reduced pressure

出典と根拠

ORDレコード
ord-b8d8d1abdc944abab613e50be801cc59
出典データセット
uspto-grants-2016_09
特許番号
US09434970B2

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