1,2-Dichloroethane → 2-(benzyloxy)-2-oxoethyl 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoate

HRID 1776514Notes

Reaction equation

HRID 1776514 reaction equation
[C:1]([O:5][C:6]([N:8]([C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[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].O[CH2:28][C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30].C(Cl)CCl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]([C:13]1[CH:21]=[CH:20][C:16]([C:17]([O:19][CH2:28][C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])=[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 3

HCID 111,2-DichloroethaneHCID 561337Benzyl 2-hydroxyacetateHCID 497657284-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoic acid

Product 1

HCID 894599242-(benzyloxy)-2-oxoethyl 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoateYield 75%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)-benzoic acid (see for reference procedure Example 18, WO 2010/089107, which is incorporated herein by reference in its entirety) (2.5 g, 6.49 mmol), benzyl 2-hydroxyacetate (1.078 g, 6.49 mmol), EDC (3.73 g, 19.46 mmol) and DMAP (0.396 g, 3.24 mmol) were mixed in DCM (150 ml), and the resulting mixture was stirred at RT for 24 hours. Then the mixture was washed with HCl 1N and NaHCO3 sat. sol.; the organic layer was dried over Na2SO4, and the solvent was evaporated. The crude was sonicated in MeOH; 2-(benzyloxy)-2-oxoethyl 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoate precipitated (2.6 g, 4.87 mmol, 75% yield, MS/ESI+ 556.0 [MNa]+), it was filtered and used as such in the following reaction without further purification.

Workup

  1. washThen the mixture was washed with HCl 1N and NaHCO3 sat. sol.
  2. dry with materialthe organic layer was dried over Na2SO4
  3. customthe solvent was evaporated
  4. customThe crude was sonicated in MeOH
  5. custom2-(benzyloxy)-2-oxoethyl 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoate precipitated (2.6 g, 4.87 mmol, 75% yield, MS/ESI+ 556.0 [MNa]+), it
  6. filtrationwas filtered
  7. customsuch in the following reaction
  8. customwithout further purification

Sources & evidence

ORD record
ord-6e615159f7c14944a01ba3ce926597df
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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