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

HRID 2222918Notes

Reaction equation

HRID 2222918 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-9977a5810db14d9b8e1e4156eeab6f8c
Source dataset
uspto-grants-2008_05
Patent number
US07371747B2

Reaction notes

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