Thioglycolic Acid → 2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoylthio)acetic acid

HRID 1776592Notes

Reaction equation

HRID 1776592 reaction equation
[C:1]([O:5][C:6]([N:8]([C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][C:14]=1[O:22][CH2:23][CH:24]1[CH2:26][CH2:25]1)[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[SH:58][CH2:59][C:60]([OH:62])=[O:61]>CN(C=O)C>[C:1]([O:5][C:6]([N:8]([C:13]1[CH:21]=[CH:20][C:16]([C:17]([S:58][CH2:59][C:60]([OH:62])=[O:61])=[O:18])=[CH:15][C:14]=1[O:22][CH2:23][CH:24]1[CH2:25][CH2:26]1)[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 1133Thioglycolic AcidHCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 497657284-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoic acid

Product 1

HCID 894599782-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoylthio)acetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoic acid (for reference procedure see Example 18, WO2010/089107, which is incorporated herein by reference in its entirety) (0.2 g, 0.519 mmol), in dry DMF (6 ml), HATU (0.198 g, 0.521 mmol) and 4-methylmorpholine (0.057 ml, 0.521 mmol) were added and the mixture was stirred at RT until the complete conversion of the carboxylic acid into the activated ester occurred. 2-mercaptoacetic acid (0.030 ml, 0.434 mmol) was then added drop-wise, and the reaction mixture was stirred in the same conditions overnight. DMF was removed under reduced pressure and the crude was partitioned between EtOAc and HCl 1N; the organic layer was dried over Na2SO4, and the resulting crude was purified by trituration with Et2O affording 2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoylthio)acetic acid as an off-white solid containing some impurities (0.253 g, yield supposed to be quantitative, MS/ESI+ 459.7 [MH]+). The product was used for the next step without any further purification.

Workup

  1. customDMF was removed under reduced pressure
  2. customthe crude was partitioned between EtOAc and HCl 1N
  3. dry with materialthe organic layer was dried over Na2SO4
  4. customthe resulting crude was purified by trituration with Et2O

Sources & evidence

ORD record
ord-02c87dd56a2d4985a976cbddd2cbd5a9
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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