Diisopropylethylamine → HCID 68999332, compound

HRID 750075Notes

Reaction equation

HRID 750075 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]2[CH:28]=[CH:27][C:13]([O:14][CH2:15][C@@H:16]3[CH2:20][CH2:19][CH2:18][N:17]3[CH2:21][CH2:22][CH2:23][C:24](O)=[O:25])=[CH:12][CH:11]=2)=[CH:5][CH:4]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:62]1([C@H:68]([NH2:70])[CH3:69])[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>ClCCl>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([O:9][C:10]2[CH:11]=[CH:12][C:13]([O:14][CH2:15][C@@H:16]3[CH2:20][CH2:19][CH2:18][N:17]3[CH2:21][CH2:22][CH2:23][C:24]([NH:70][C@@H:68]([C:62]3[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=3)[CH3:69])=[O:25])=[CH:27][CH:28]=2)=[CH:7][CH:8]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 6431891-Phenethylamine, (+)-HCID 2733179PyBroPHCID 44818987DG 051 (HCl salt)

Product 1

HCID 68999332HCID 68999332, compoundYield 27.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-{(S)-2-[4-(4-chloro-phenyoxy)-phenoxymethyl]-pyrrolidin-1-yl}-butyric acid HCl salt (220 mg, 0.5 mmol, 1 eq.) in dichloromethane (5 ml) was added PyBrOP (280 mg, 0.6 mmol, 1.2 eq.), DIPEA (200 mg, 1.5 mmol, 3 eq.) and (R)-1-phenyl ethylamine (80 mg, 0.6 mmol 1.2 eq.). The mixture was stirred at room temperature for 24 h. The mixture was poured onto 30 mL ice-water solution and this solution was extracted with EtOAc (3×30 mL). The combined organic layers were washed with water (2×30 mL), brine (30 mL) and dried over anhy. Na2SO4. The solvent was removed in vacuo to provide the crude product which was purified by silica gel flash chromatography to afford the title product (68 mg, 25%); LCMS; 95%; APCI+, Calcd 493.05. Found m/z 493.2 (M). 1H NMR (400 MHz, CDCL3); δ 1.47 (d, J=5.6 Hz, 3H), 1.52-2.01 (m, 6H), 2.21-2.59 (m, 4H), 2.79-2.98 (m, 2H), 3.12-3.23 (m, 1H), 3.68-3.89 (m, 2H), 5.10-5.17 (m, 1H), 6.81 (d, J=9.2 Hz, 2H), 6.86 (d, J=9.2 Hz, 2H), 6.92 (d, J=9.2 Hz, 2H), 7.22-7.26 (m, 5H), 7.29 (d, J=4.4 Hz, 2H).

Workup

  1. extractionthis solution was extracted with EtOAc (3×30 mL)
  2. washThe combined organic layers were washed with water (2×30 mL), brine (30 mL)
  3. customdried over anhy
  4. customThe solvent was removed in vacuo
  5. customto provide the crude product which
  6. customwas purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-d5647365c65a4f23880e7c55555066ac
Source dataset
uspto-grants-2008_07
Patent number
US07402684B2

Reaction notes

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