1(3H)-Isobenzofuranone, 3-bromo- → HCID 68720237, compound

HRID 2246699Notes

Reaction equation

[C:1]([O:5][C:6]([NH:8][CH2:9][C@@H:10]([OH:22])[CH2:11][P:12]([CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)(=[O:14])[OH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH:24]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26](=[O:33])[O:25]1>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[O:33]=[C:26]1[C:27]2[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:24]([O:14][P:12]([CH2:11][C@H:10]([OH:22])[CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])([CH2:15][CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)=[O:13])[O:25]1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of ((R)-3-tert-butoxycarbonylamino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid (0.5 g, 1.49 mmol) in 30 mL toluene was added 3-bromo-3H-isobenzofuran-1-one (952 mg, 4.47 mmol) and silver carbonate (1.23 g, 4.47 mmol). The reaction mixture was heated to 120° C. for 2 h. After filtering hot and concentrating in vacuo the crude product was purified by gradient flash chromatography (methanol/methylene chloride) on a 35 g RediSep disposable column to give ((R)-3-tert-butoxycarbonylamino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid 3-oxo-1,3-dihydro-isobenzofuran-1-yl ester (150 mg, 0.32 mmol). 1H NMR (CDCl3, 300 MHz): δ 7.92 (m, 1H), 7.73 (m, 2H), 7.12 (m, 1H), 5.1 (m, 1H), 4.40 (m, 1H), 4.2 (m, 1H), 3.4-3.22 (m, 1H), 3.20-3.04 (m, 1H), 2.01-1.58 (m, 10H), 1.48 (s, 9H), 1.40-0.95 (m, 6H). LC/MS m/z: [M+H]+=468.

Workup

filtrationAfter filtering hot
concentrationconcentrating in vacuo the crude product
customwas purified by gradient flash chromatography (methanol/methylene chloride) on a 35 g RediSep disposable column

Sources & evidence

ORD record: ord-5b974c5377ba4c73908df36785d2ae85
Source dataset: uspto-grants-2010_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07687540B2

Reaction notes

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