Glycolic Acid → (S)-N-[3-(4-cyano-2-ethyl-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamide

HRID 1958786Notes

Reaction equation

HRID 1958786 reaction equation
[NH2:1][CH2:2][C@H:3]([OH:17])[CH2:4][O:5][C:6]1[C:13]([CH3:14])=[CH:12][C:9]([C:10]#[N:11])=[CH:8][C:7]=1[CH2:15][CH3:16].[C:18](O)(=[O:21])[CH2:19][OH:20].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C([O-])(O)=O.[Na+]>[C:10]([C:9]1[CH:12]=[C:13]([CH3:14])[C:6]([O:5][CH2:4][C@@H:3]([OH:17])[CH2:2][NH:1][C:19](=[O:20])[CH2:18][OH:21])=[C:7]([CH2:15][CH3:16])[CH:8]=1)#[N:11]

Participants

6

Reactant 4

HCID 757Glycolic AcidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 66932187(S)-4-(3-amino-2-hydroxypropoxy)-3-ethyl-5-methylbenzonitrile

Product 1

HCID 66932427(S)-N-[3-(4-cyano-2-ethyl-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamideYield 90.4%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (S)-4-(3-amino-2-hydroxypropoxy)-3-ethyl-5-methylbenzonitrile (6.23 g, 26.59 mmol), glycolic acid (2.43 g, 31.9 mmol), HOBt (4.31 g, 31.9 mmol), and EDC hydrochloride (6.12 g, 31.9 mmol) were added. The mixture was stirred at rt for 18 h before it was diluted with sat. aq. NaHCO3 and extracted twice with EA. The combined org. extracts were dried over MgSO4, filtered and concentrated. The crude product was purified by CC with DCM containing 8% of MeOH to give (S)—N-[3-(4-cyano-2-ethyl-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamide as a yellow oil (7.03 g). LC-MS: tR=0.74 min; [M+1]+=293.10; 1H NMR (CDCl3): δ 1.25 (t, J=7.5 Hz, 3H), 2.32 (s, 3H), 2.69 (q, J=7.5 Hz, 2H), 3.48-3.56 (m, 3H), 3.70-3.90 (m, 3H), 4.19 (br s, 3H), 7.06 (m, 1H), 7.36 (s, 1H), 7.38 (s, 1H).

Workup

  1. extractionextracted twice with EA
  2. dry with materialextracts were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by CC with DCM containing 8% of MeOH

Sources & evidence

ORD record
ord-f3f6a9fee2d84183854f92a069fef1f2
Source dataset
uspto-grants-2013_04
Patent number
US08410151B2

Reaction notes

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