Triethylamine → (5r/s,6r/s)-n-(Cyanomethyl)-6-{[(4-fluorophenyl)sulfanyl]methyl}spiro[2.4]-heptane-5-carboxamide

HRID 2222918ノート

反応式

HRID 2222918 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH:10]2[CH2:16][C:13]3([CH2:15][CH2:14]3)[CH2:12][CH:11]2[C:17]([OH:19])=O)=[CH:4][CH:3]=1.Cl.[NH2:21][CH2:22][C:23]#[N:24].F[P-](F)(F)(F)(F)F.N1([PH+](N2CCCC2)N2CCCC2)CCCC1.C(N(CC)CC)C>CN(C)C=O>[C:22]([CH2:23][NH:24][C:17]([CH:11]1[CH:10]([CH2:9][S:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[CH2:16][C:13]2([CH2:14][CH2:15]2)[CH2:12]1)=[O:19])#[N:21]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 11491918Aminoacetonitrile hydrochlorideHCID 22226026Tripyrrolidinophosphonium hexafluorophosphateHCID 69679911(5r/s,6r/s)-6-{[(4-Fluorophenyl)sulfanyl]-methyl}spiro[2.4]heptane-5-carboxylic acid

生成物 1

HCID 59711755(5r/s,6r/s)-n-(Cyanomethyl)-6-{[(4-fluorophenyl)sulfanyl]methyl}spiro[2.4]-heptane-5-carboxamide

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To (5R/S,6R/S)-6-{[(4-fluorophenyl)sulfanyl]methyl}spiro[2.4]heptane-5-carboxylic acid (59 mg, 0.21 mmol) was added aminoacetonitrile hydrochloride (30 mg, 0.32 mmol) and benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (120 mg, 0.23 mmol) and dimethylformamide (0.70 mL). The reaction mixture was cooled to 0° C. and triethylamine (90 PL, 0.65 mmol) was added. After stirring for 11 h, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and concentrated. Chromatography of the residue on silica gel with 35:65 ethyl acetate:hexanes provided the title compound as a of a colorless, waxy solid. 1H NMR (500 MHz, acetone-d6): δ=7.76 (1H, br s), 7.40 (2H, dd), 7.08 (2H, t), 4.22 (2H, d), 3.15 (1H, dd), 2.93 (1H, dd), 2.75 (1H, dd), 2.66 (1H, m), 1.90 (1H, dd), 1.86 (1H, dd), 1.50 (1H, dd), 0.45 (4H, m). MS [APCI, (M−H)−] m/z=317.0 amu.

後処理

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. customThe organic layer was separated
  3. washwashed with saturated sodium chloride aqueous solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated

出典と根拠

ORDレコード
ord-9977a5810db14d9b8e1e4156eeab6f8c
出典データセット
uspto-grants-2008_05
特許番号
US07371747B2

反応ノート

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