Glycolic Acid → HCID 59497890, compound

HRID 1676137Notes

Reaction equation

HRID 1676137 reaction equation
[NH2:1][CH2:2][CH:3]([OH:28])[CH2:4][O:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([CH2:13][CH2:14][C:15]([C:17]2[S:18][CH:19]=[C:20]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:21]=2[CH3:22])=[O:16])=[CH:8][C:7]=1[CH3:27].[C:29](O)(=[O:32])[CH2:30][OH:31].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[OH:32][CH2:29][C:30]([NH:1][CH2:2][CH:3]([OH:28])[CH2:4][O:5][C:6]1[C:11]([CH3:12])=[CH:10][C:9]([CH2:13][CH2:14][C:15]([C:17]2[S:18][CH:19]=[C:20]([CH2:23][CH:24]([CH3:26])[CH3:25])[C:21]=2[CH3:22])=[O:16])=[CH:8][C:7]=1[CH3:27])=[O:31]

Participants

6

Reactant 4

HCID 757Glycolic AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 59497921HCID 59497921, compound

Product 1

HCID 59497890HCID 59497890, compoundYield 39.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of rac-3-[4-(3-amino-2-hydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(4-isobutyl-3-methyl-thiophen-2-yl)-propan-1-one (353 mg, 0.876 mmol) in DCM (10 mL), glycolic acid (127 mg, 1.67 mmol) followed by DIPEA (521 mg, 4.03 mmol) and TBTU (439 mg, 1.37 mmol) is added and the reaction mixture is stirred at rt for 16 h. The mixture is diluted with DCM and washed twice with water. The aq. washings are extracted three times with DCM. The combined organic extracts are dried over MgSO4, filtered and evaporated. The crude product is purified by CC on silica gel eluting with EA containing 0 to 100% of MeOH to give racemic 2-hydroxy-N-(2-hydroxy-3-{4-[3-(4-isobutyl-3-methyl-thiophen-2-yl)-3-oxo-propyl]-2,6-dimethyl-phenoxy}-propyl)-acetamide (160 mg) as a beige solid; LC-MS: tR=0.99 min, [M+1]=462.40; 1H NMR (D6-DMSO): δ 7.66 (t, J=5.9 Hz, 1H), 7.45 8s, 1H), 6.86 (s, 2H), 5.63 (s br, 1H), 5.26 (s br, 1H), 3.91-3.83 (m, 1H), 3.79 (s, 2H), 3.63-3.55 (m, 2H), 3.45-3.36 (m, 1H), 3.22-3.12 (m 1H), 0.310-3.04 (m, 2H), 2.80-2.73 (m, 2H), 2.40-2.37 (m, 5H), 2.15 (s, 6H), 1.76 (m, J=7.0 Hz, 1H), 0.85 (d, J=6.4 Hz, 6H).

Workup

  1. additionis added
  2. washwashed twice with water
  3. extractionThe aq. washings are extracted three times with DCM
  4. dry with materialThe combined organic extracts are dried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude product is purified by CC on silica gel eluting with EA containing 0 to 100% of MeOH

Sources & evidence

ORD record
ord-2a339848218c425fa30c2c127ae37329
Source dataset
uspto-grants-2011_08
Patent number
US08003800B2

Reaction notes

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