Hydrochloric Acid → (S)-2-(4-fluoro-3,5-dimethylbenzyl)-6-(4-fluoro-3-methylbenzyloxy)-N-hydroxyhexanamide

HRID 1158135Notes

Reaction equation

HRID 1158135 reaction equation
[F:1][C:2]1[C:38]([CH3:39])=[CH:37][C:5]([CH2:6][C@H:7]([CH2:23][CH2:24][CH2:25][CH2:26][O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[C:31]([CH3:36])[CH:30]=2)[C:8]([N:10]2[C@H](CC3C=CC=CC=3)COC2=O)=[O:9])=[CH:4][C:3]=1[CH3:40].[C-]#N.[K+].Cl.C1C[O:48]CC1.CO>>[F:1][C:2]1[C:38]([CH3:39])=[CH:37][C:5]([CH2:6][C@H:7]([CH2:23][CH2:24][CH2:25][CH2:26][O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([F:35])=[C:31]([CH3:36])[CH:30]=2)[C:8]([NH:10][OH:48])=[O:9])=[CH:4][C:3]=1[CH3:40]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 9032Potassium CyanideHCID 21899815MeOH tetrahydrofuranHCID 59512593(R)-3-((S)-2-(4-fluoro-3,5-dimethylbenzyl)-6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-one

Product 1

HCID 54584001(S)-2-(4-fluoro-3,5-dimethylbenzyl)-6-(4-fluoro-3-methylbenzyloxy)-N-hydroxyhexanamideYield 23%

Procedure

To a solution of (R)-3-((S)-2-(4-fluoro-3,5-dimethylbenzyl)-6-(4-fluoro-3-methylbenzyloxy)hexanoyl)-4-benzyloxazolidin-2-one (0.040 g, 0.0728 mmol) in 2.5 mL of THF/MeOH/50% NH2OH—H2O (2:2:1), KCN (0.001 g, 0.015 mmol) was added. After stirring at room temperature for overnight, the reaction mixture was acidified with concentrated HCl to pH=2 and filtered. The filtrate was purified by RP-HPLC eluting with 20-100% acetonitrile (0.025% TFA)/water (0.025% TFA) to give the title compound as an off-white solid (0.005 g, 23% yield). LC-MS: tR=9.6 min, m/z 406 (M+H)+; 1H NMR (300 MHz, CD3OD) δ 1.28-1.51 (m, 4H), 1.52-1.70 (m, 2H), 2.18 (s, 6H), 2.25 (s, 3H), 2.26-2.33 (m, 1H), 2.52-2.63 (m, 1H), 2.68-2.79 (m, 1H), 3.44 (t, J=6.30 Hz, 2H), 4.40 (s, 2H), 6.81 (d, J=7.03 Hz, 2H), 6.97 (t, J=9.08 Hz, 1H), 7.09-7.15 (m, 1H), 7.18 (d, J=7.32 Hz, 1H).

Workup

  1. filtrationfiltered
  2. customThe filtrate was purified by RP-HPLC
  3. washeluting with 20-100% acetonitrile (0.025% TFA)/water (0.025% TFA)

Sources & evidence

ORD record
ord-8062158b9b9644a8a993bc15d08c5b14
Source dataset
uspto-grants-2010_10
Patent number
US07807720B2

Reaction notes

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