2-(Bromomethyl)pyrimidine → 3-(Pyrimidin-2-yl)-2,2-bis(3-(trifluoromethoxy)phenyl)propanoic acid

HRID 238791Notes

Reaction equation

[F:1][C:2]([F:26])([F:25])[O:3][C:4]1[CH:5]=[C:6]([CH:10]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=2)[C:11]([OH:13])=[O:12])[CH:7]=[CH:8][CH:9]=1.[Li]CCCC.Br[CH2:33][C:34]1[N:39]=[CH:38][CH:37]=[CH:36][N:35]=1>C1COCC1>[N:35]1[CH:36]=[CH:37][CH:38]=[N:39][C:34]=1[CH2:33][C:10]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=1)([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:25])([F:26])[F:1])[CH:5]=1)[C:11]([OH:13])=[O:12]

Participants

Conditions

Temperature: -15 °C

Procedure

At −15° C. to a solution of 2,2-bis(3-(trifluoromethoxy)phenyl)acetic acid prepared as described in Procedure 73 (607 mg, 1.6 mmol) in THF (6 mL) was added nBuLi (1.6 mL, 2M in hexane, 3.2 mmol). The mixture was stirred at −15° C. for 45 min. 2-(Bromomethyl)pyrimidine (412 mg, crude) in THF (1 mL) was added and the reaction mixture was allowed to warm to rt and stirred for 18 h, then quenched with saturated NH4Cl. The aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layer was dried over MgSO4, filtered and concentrated to give 3-(pyrimidin-2-yl)-2,2-bis(3-(trifluoromethoxy)phenyl)propanoic acid as a yellow solid (437 mg, 58% crude). This crude solid was carried onto the next step without further purification.

Workup

temperatureto warm to rt
stirringstirred for 18 h
customquenched with saturated NH4Cl
extractionThe aqueous layer was extracted with EtOAc (3×50 mL)
dry with materialThe combined organic layer was dried over MgSO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-7e2d30e41aa54d919f665d27594cf36f
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08642576B2

Reaction notes

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