Thioglycolic Acid → (S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-((S)-1-phenyl-propylamino)-propionic acid methyl ester

HRID 708573Notes

Reaction equation

HRID 708573 reaction equation
[CH3:1][O:2][C:3](=[O:54])[C@@H:4]([N:32](S(C1C=CC([N+]([O-])=O)=CC=1)(=O)=O)[C@H:33]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH2:34][CH3:35])[CH2:5][C:6]1[CH:31]=[CH:30][C:9]2[O:10][C@@H:11]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=4)=[CH:16][CH:15]=3)[CH2:12][O:13][C:8]=2[CH:7]=1.SCC(O)=O.C1CCN2C(=NCCC2)CC1>CN(C=O)C>[CH3:1][O:2][C:3](=[O:54])[C@@H:4]([NH:32][C@H:33]([C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)[CH2:34][CH3:35])[CH2:5][C:6]1[CH:31]=[CH:30][C:9]2[O:10][C@@H:11]([C:14]3[CH:15]=[CH:16][C:17]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=4)=[CH:18][CH:19]=3)[CH2:12][O:13][C:8]=2[CH:7]=1

Participants

5

Reactant 3

HCID 1133Thioglycolic AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 66719419(S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-[(4-nitro-benzenesulfonyl)-((S)-1-phenyl-propyl)-amino]-propionic acid methyl ester

Product 1

HCID 58327321(S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-((S)-1-phenyl-propylamino)-propionic acid methyl esterYield 64.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(S)-3-{(S)-2-[4-(3,4-Dichloro-benzyloxy)-phenyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-2-[(4-nitro-benzenesulfonyl)-((S)-1-phenyl-propyl)-amino]-propionic acid methyl ester (1.8 g) was dissolved in 30 mL dry DMF, then 505 μL (670 mg) mercaptoacetic acid and 2.6 mL (2.6 g) DBU were added at rt. The reaction stirred for 3 h, then was partitioned between saturated aqueous NaHCO3 and diethyl ether. The organic layer was washed successively with aqueous NaHCO3, water, and brine, then was dried with Na2SO4 and evaporated. The residue was purified by silica gel flash chromatography (9:1 to 8:2 hexanes/EtOAc) to give 893 mg desired product after drying. 1H NMR (400 MHz, acetone-d6): 7.71 (d, 1H), 7.61 (d, 1H), 7.50-7.42 (m, 3H), 7.27-7.15 (m, 5H), 7.09 (m, 2H), 6.80 (d, 1H), 6.67 (d, 1H), 6.61 (m, 1H), 5.19 (s, 2H), 5.10 (m, 1H), 4.34 (m, 1H), 4.02 (m, 1H), 3.63 (s, 3H), 3.47 (t, 1H), 3.15 (t, 1H), 2.75 (m, 2H), 2.10 (s, 1H), 1.69-1.48 (m, 2H), 0.78 (t, 3H).

Workup

  1. customwas partitioned between saturated aqueous NaHCO3 and diethyl ether
  2. washThe organic layer was washed successively with aqueous NaHCO3, water, and brine
  3. dry with materialwas dried with Na2SO4
  4. customevaporated
  5. customThe residue was purified by silica gel flash chromatography (9:1 to 8:2 hexanes/EtOAc)

Sources & evidence

ORD record
ord-8428988fafa545379ae815eed7e7956c
Source dataset
uspto-grants-2015_11
Patent number
US09175003B2

Reaction notes

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