Hydrochloric Acid → {(3S)-3-[(benzylamino)methyl]-6-nitro-2,3-dihydro-1,4-benzodioxin-5-yl}acetonitrile

HRID 1259460Notes

Reaction equation

HRID 1259460 reaction equation
CC(C)([O-])C.[K+].[CH2:7]([NH:14][CH2:15][C@@H:16]1[O:21][C:20]2[CH:22]=[C:23]([N+:26]([O-:28])=[O:27])[CH:24]=[CH:25][C:19]=2[O:18][CH2:17]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.ClC1C=CC(O[CH2:35][C:36]#[N:37])=CC=1.Cl>CN(C=O)C>[CH2:7]([NH:14][CH2:15][C@H:16]1[CH2:17][O:18][C:19]2[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[C:22]([CH2:35][C:36]#[N:37])[C:20]=2[O:21]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 3064442-(4-Chlorophenoxy)acetonitrileHCID 23665647Potassium tert-butoxideHCID 25019977HCID 25019977, compound

Product 1

HCID 25019979{(3S)-3-[(benzylamino)methyl]-6-nitro-2,3-dihydro-1,4-benzodioxin-5-yl}acetonitrileYield 90.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A 250 mL round bottomed flask equipped with a magnetic stir bar is charged with solid 95% potassium t-butoxide (1.57 g, 13.5 mmol) and DMF (6.5 mL), and the suspension is stirred until all the solids are dissolved. A DMF (4.0 mL) solution containing N-benzyl-1-[(2S)-7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methanamine (1.00 g, 3.3 mmol) and (4-chlorophenoxy)acetonitrile (1.12 g, 6.7 mmol) is added over 3 min. After 30 min, a 2 N aqueous solution of HCl is added until pH 1 is obtained (˜9 mL). The solution is transferred to a separatory funnel and extracted with toluene (2×10 mL) and discarded. The product-containing aqueous phase is adjusted to pH 10 by the addition of 10 N aqueous NaOH, and extracted with toluene (2×10 mL). The product-containing organic phases are combined and washed with water (15 mL) and then with brine (15 mL), and the volatiles are removed by evaporation to give the title compound (1.01 g, 88%) as a syrup. LCMS (Basic Method): 2.06 min, 340 (M+H)+. 1H NMR (300 MHz, DMSO-d6) δ 7.71 (d, J=9.1 Hz, 1H), 7.35-7.17 (m, 5H), 7.10 (d, J=9.1 Hz, 1H), 4.50-4.37 (m, 2H), 4.16 (dd, J=7.0, 11.4 Hz, 1H), 4.10 (s, 2H), 3.76 (s, 2H), 2.87-2.74 (m, 2H), NH not observed.

Workup

  1. customA 250 mL round bottomed flask equipped with a magnetic stir bar
  2. dissolutionare dissolved
  3. additionis added over 3 min
  4. customis obtained (˜9 mL)
  5. customThe solution is transferred to a separatory funnel
  6. extractionextracted with toluene (2×10 mL)
  7. additionThe product-containing aqueous phase is adjusted to pH 10 by the addition of 10 N aqueous NaOH
  8. extractionextracted with toluene (2×10 mL)
  9. washwashed with water (15 mL)
  10. customwith brine (15 mL), and the volatiles are removed by evaporation

Sources & evidence

ORD record
ord-f2a809aaf37143839d36d8ba926fe58a
Source dataset
uspto-grants-2013_06
Patent number
US08466296B2

Reaction notes

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