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

HRID 245091Notes

Reaction equation

HRID 245091 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>C1COCC1.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

7

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 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of (S)-4-(3-amino-2-hydroxypropoxy)-3-ethyl-5-methylbenzonitrile (6.23 g, 26.59 mmol) in THF (150 mL), glycolic acid (2.43 g, 31.9 mmol), HOBt (4.31 g, 31.9 mmol), and EDC hydrochloride (6.12 g, 31.9 mmol) are added. The mixture is stirred at rt for 18 h before it is diluted with sat. aq. NaHCO3 and extracted twice with EA. The combined org. extracts are dried over MgSO4, filtered and concentrated. The crude product is purified by CC with DCM containing 8% of methanol to give (S)—N-[3-(4-cyano-2-ethyl-6-methyl-phenoxy)-2-hydroxy-propyl]-2-hydroxy-acetamide (7.03 g) as a yellow oil; 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 (s, br, 3H), 7.06 (m, 1H), 7.36 (s, 1H), 7.38 (s, 1H).

Workup

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

Sources & evidence

ORD record
ord-8fa78837f05247f3931f16327f9792fc
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

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