Dichloromethane → 3-{4-[4-(2-amino-3-morpholin-4-yl-3-oxopropyl)-phenoxy]-phenyl}-N-hydroxypropionamide hydrochloride

HRID 748989Notes

Reaction equation

HRID 748989 reaction equation
C(OC(=O)[NH:7][CH:8]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33](=[O:36])[NH:34][OH:35])=[CH:27][CH:26]=2)=[CH:20][CH:19]=1)[C:9]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[O:10])(C)(C)C.C(Cl)[Cl:39]>>[ClH:39].[NH2:7][CH:8]([C:9]([N:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1)=[O:10])[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([CH2:31][CH2:32][C:33]([NH:34][OH:35])=[O:36])=[CH:27][CH:26]=2)=[CH:20][CH:19]=1

Participants

3

Reactant 2

HCID 6344DichloromethaneHCID 59762804(1-{4-[4-(2-Hydroxycarbamoyl-ethyl)-phenoxy]-benzyl}-2-morpholin-4-yl-2-oxoethyl)-carbamic acid tert-butyl ester

Product 1

HCID 159825743-{4-[4-(2-amino-3-morpholin-4-yl-3-oxopropyl)-phenoxy]-phenyl}-N-hydroxypropionamide hydrochlorideYield 85%

Conditions

Temperature
2.5 °C

Procedure

The compound 16 (1.1 g) was dissolved in CH2Cl2 (30 mL) and cooled to 0-5° C. Hydrogen chloride gas was bubbled through this solution for 20 min. The bubbling was discontinued and the reaction mixture was stirred at room temperature for 1 h. The excess HCl was degassed and the CH2Cl2 was removed. The residual solid was triturated with EtOAc (2×25 mL), decanted, and dried to yield the desired compound 17 as a white amorphous solid (0.82 g, 85%). 1H NMR (400 MHz, DMSO-d6): 10.40 (s, 1H), 7.23 (overlapped d, J=8.8 Hz, 2H), 7.20 (overlapped d, J=8.8 Hz, 2H), 6.96 (d, J=8.4 Hz, 2H), 6.89 (d, J=8.4 Hz, 2H), 4.62 (m, 1H), 3.35-3.54 (m, 8H), 2.91-3.07 (m, 2H), 2.80 (t, J=8.0 Hz, 2H), 2.25 (t, J=8.0 Hz, 2H); LCMS: Obsd.414, Calcd. 413.47.

Workup

  1. customHydrogen chloride gas was bubbled through this solution for 20 min
  2. customThe excess HCl was degassed
  3. customthe CH2Cl2 was removed
  4. customThe residual solid was triturated with EtOAc (2×25 mL)
  5. customdecanted
  6. customdried

Sources & evidence

ORD record
ord-235fc3b53c5244aead12ace6ad9edc38
Source dataset
uspto-grants-2008_07
Patent number
US07399786B2

Reaction notes

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