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Sodium Hydroxide → (RS)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

HRID 1058787
ノート
印刷プレビュー

反応式

HRID 1058787 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:26]2[CH:31]=[CH:30][C:29]([CH:32]=O)=[CH:28][CH:27]=2)[N:9]2[CH2:12][C:11](=[C:13]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=3)[S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10]2)=[CH:4][CH:3]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[NH:48]1[CH2:52][CH2:51][CH2:50][CH2:49]1.[OH-].[Na+]>ClCCCl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:26]2[CH:31]=[CH:30][C:29]([CH2:32][N:48]3[CH2:52][CH2:51][CH2:50][CH2:49]3)=[CH:28][CH:27]=2)[N:9]2[CH2:12][C:11](=[C:13]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=3)[S:14]([CH3:17])(=[O:16])=[O:15])[CH2:10]2)=[CH:4][CH:3]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 14798Sodium HydroxideHCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 22506638(-)-1-[(4-Chlorophenyl)(4-formylphenyl)methyl]-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine

生成物 1

HCID 10280566(RS)-1-{(4-chlorophenyl)[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine
収率 51.1%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒

実験手順

0.75 g of (RS)-1-{(4-chlorophenyl)(4-formylphenyl)methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine and then 0.68 g of sodium triacetoxyborohydride are added to a solution of 0.10 g of pyrrolidine in 20 cm3 of 1,2-dichloroethane. After 20 hours at room temperature, 2 cm3 of 1 N sodium hydroxide are added, the product is extracted with 100 cm3 of dichloromethane, the organic phase is washed twice with 50 cm3 of water and then 50 cm3 of a saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained is chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 4.1 cm, height 13 cm), at an argon pressure of 0.5 bar with acetate as eluent and collecting 20 cm3 fractions. Fractions 10 to 18 are combined and then concentrated to dryness under reduced pressure (2.7 kPa). 0.39 g of (RS)-1-{(4-chlorophenyl)-[4-(pyrrolidylmethyl)phenyl]methyl}-3-[(3,5-difluorophenyl)(methylsulfonyl)methylene]azetidine is obtained in the form of a white foam [NMR spectrum in DMSO-d6, T=300K, δ in ppm (300 MHz): 1.65 (4H, m, 2CH2), 2.40 (4H,m, 2NCH2), 3.02 (3H,s, SCH3), 3.50 (2H, s, NCH2Ph), 3.85 (2H, s, NCH2), 4.20 (2H, S, NCH2), 4.75 (1H, s, NCH), between 7.15 and 7.40 (9H, m, 9CH arom.), 7.48 (2H, d, J=7 Hz, 2CH arom.)].

後処理

  1. extractionthe product is extracted with 100 cm3 of dichloromethane
  2. washthe organic phase is washed twice with 50 cm3 of water
  3. dry with material50 cm3 of a saturated sodium chloride solution, dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  6. customThe residue obtained
  7. customis chromatographed on a silica gel column (particle size 0.04-0.06 mm, diameter 4.1 cm, height 13 cm), at an argon pressure of 0.5 bar with acetate as eluent
  8. customcollecting 20 cm3 fractions
  9. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

出典と根拠

ORDレコード
ord-418328b0eeea45989fa080462effeb44
出典データセット
uspto-grants-2003_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06518264B2

反応ノート

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