tert-Butyl bromoacetate → Tert-butyl 2-(4-(thiophene-2-sulfonamido)naphthalen-1-yloxy)acetate

HRID 1258394Notes

Reaction equation

HRID 1258394 reaction equation
[OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([NH:12][S:13]([C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)(=[O:15])=[O:14])=[CH:4][CH:3]=1.Br[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].C1CCN2C(=NCCC2)CC1>CN(C=O)C.C(OCC)(=O)C>[S:17]1[CH:18]=[CH:19][CH:20]=[C:16]1[S:13]([NH:12][C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]([O:1][CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:3][CH:4]=1)(=[O:15])=[O:14]

Participants

6

Reactant 3

HCID 79177tert-Butyl bromoacetate2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 697391N-(4-hydroxynaphthalen-1-yl)thiophene-2-sulfonamide

Product 1

HCID 46908189Tert-butyl 2-(4-(thiophene-2-sulfonamido)naphthalen-1-yloxy)acetateYield 51.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

61.1 mg 3 was dissolved in 1 ml DMF, to which was added 60 μl tert-butyl bromoacetate followed by 0.4 ml DBU solution (1M in NMP) and catalytic amount of KI. The mixture was heated with microwave initiator (biotage) to 90° C. and reacted for 20 min. TLC indicated the reaction didn't go complete. Additional 13.5 eq. of tert-butyl bromoacetate was added. The mixture was continued at 90° C. for 30 min. The mixture was diluted with ethyl acetate to 40 ml and washed with 0.5 M NaHSO4, H2O and brine. Dried over Na2SO4, the organic phase was concentrated and the residue was purified via flash chromatography (5 g silica gel, Hex/EtOAc) affording 43 mg (51.3%) solid. 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J=7.8 Hz, 1H), 7.80 (dd, J=8.1, 1.2 Hz, 1H), 7.61 (dd, J=5.0, 1.3 Hz, 1H), 7.56 (dd, J=3.8, 1.3 Hz, 1H), 7.46-7.36 (m, 2H), 7.16 (d, J=8.4 Hz, 1H), 6.99 (dd, J=5.0, 3.8 Hz, 1H), 6.31 (d, J=8.4 Hz, 1H), 3.92 (s, 2H), 1.52 (s, 9H).; LRMS (ES+) 420 (M+H)+; HRMS (ES+) m/z calculated for C20H22NO5S2 (M+H)+ 420.0934, found 420.0932.

Workup

  1. customreacted for 20 min
  2. customthe reaction didn't go complete
  3. washwashed with 0.5 M NaHSO4, H2O and brine
  4. dry with materialDried over Na2SO4
  5. concentrationthe organic phase was concentrated
  6. customthe residue was purified via flash chromatography (5 g silica gel, Hex/EtOAc)

Sources & evidence

ORD record
ord-196adba5c37e49b0b75466a43e188c30
Source dataset
uspto-grants-2013_06
Patent number
US08466157B2

Reaction notes

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