Ethyl Acetate → HCID 51348668, compound

HRID 454988Notes

Reaction equation

[OH:1][CH2:2][C@@H:3]([C:15]1[CH:20]=[CH:19][C:18](OS(C(F)(F)F)(=O)=O)=[CH:17][C:16]=1[O:29][CH3:30])[NH:4][C:5]([C@H:7]1[CH2:9][C@@H:8]1[C:10]1[S:11][CH:12]=[CH:13][CH:14]=1)=[O:6].[C:31]1([CH3:40])[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:1][CH2:2][C@H:3]([NH:4][C:5]([C@H:7]1[CH2:9][C@@H:8]1[C:10]1[S:11][CH:12]=[CH:13][CH:14]=1)=[O:6])[C:15]1[CH:20]=[CH:19][C:18]([C:34]2[CH:35]=[CH:36][C:31]([CH3:40])=[CH:32][CH:33]=2)=[CH:17][C:16]=1[O:29][CH3:30]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of trifluoro-methanesulfonic acid 4-{(R)-2-hydroxy-1-[((1S,2S)-2-thiophen-2-yl-cyclopropanecarbonyl)amino]-ethyl}-3-methoxy-phenyl ester (66 mg, 0.142 mmol), tolylboronic acid (38.1 mg, 0.284 mmol), Pd(PPh3)4 (16.4 mg, 0.014 mmol) and Na2CO3 (45.2 mg, 0.426 mmol) in DME/H2O (1.2/0.4 mL) was heated at 80° C. for 3 h. The reaction mixture was passed through a short silica pad (EtOAc) and concentrated. The residue was subjected to preparative HPLC to give the titled compound (12.3 mg). 1H NMR (400 MHz, MeOD) δ ppm 7.7 (d, J=8.3 Hz, 2H), 7.6 (d, J=8.3 Hz, 1H), 7.5 (d, J=7.8 Hz, 2H), 7.4 (t, J=5.4 Hz, 2H), 7.1-7.2 (m, 1H), 7.1 (d, J=3.5 Hz, 1H), 5.6 (dd, J=7.8, 4.5 Hz, 1H), 4.8 (s, 1H), 4.2 (s, 3H), 4.0 (dd, J=11.1, 4.5 Hz, 1H), 3.9 (dd, J=11.4, 7.8 Hz, 1H), 2.8 (dd, J=6.3, 2.5 Hz, 1H), 2.6 (s, 3H), 2.3 (dd, J=8.0, 4.7 Hz, 1H), 1.8 (ddd, J=9.2, 4.8, 4.7 Hz, 1H), 1.5 (ddd, 1H). LRMS (ESI)=408, [(M+1)+ calcd for C24H26NO3S 407.5].

Workup

concentrationconcentrated

Sources & evidence

ORD record: ord-2009e0d6effb4146aadc70eb1a824171
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497271B2

Reaction notes

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