Formaldehyde → 3-(2-Chloro-4-methylamino-phenyl)-2-(2-chloro-pyridin-4-yl)-1,1,1-trifluoro-butan-2-ol

HRID 1095914Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:22])[C:9]([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([Cl:21])[CH:16]=2)([OH:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([Cl:23])[CH:3]=1.[CH2:24]=O.C[O-].[Na+].[BH4-].[Na+]>CO.O>[Cl:23][C:4]1[CH:3]=[C:2]([NH:1][CH3:24])[CH:7]=[CH:6][C:5]=1[CH:8]([CH3:22])[C:9]([C:15]1[CH:20]=[CH:19][N:18]=[C:17]([Cl:21])[CH:16]=1)([OH:14])[C:10]([F:11])([F:12])[F:13]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 3-(4-amino-2-chloro-phenyl)-2-(2-chloro-pyridin-4-yl)-1,1,1-trifluoro-butan-2-ol (Example 68 step 4, 50 mg) in MeOH (14 ml) and paraformaldehyde (21 mg) was added to a suspension of NaOMe (44 mg) in MeOH (1 ml). The mixture was heated for 2 h under reflux and then cooled to 0° C. NaBH4 (29 mg) was added and the mixture was stirred for 1.5 h at room temperature. Additional NaBH4 (78 mg) was added and the mixture heated 30 min under reflux. Water (30 ml) was added and extracted with DCM. The combined organic layers were dried over Na2SO4 and then concentrated to an oil. The residue was purified by flash chromatography (SiO2, 0 to 30% EtOAc/heptane) to give the title compound (19 mg) as a light yellow foam. MS (m/e)=379.1 [M+H+].

Workup

temperatureThe mixture was heated for 2 h
temperatureunder reflux
temperaturethe mixture heated 30 min
temperatureunder reflux
extractionextracted with DCM
dry with materialThe combined organic layers were dried over Na2SO4
concentrationconcentrated to an oil
customThe residue was purified by flash chromatography (SiO2, 0 to 30% EtOAc/heptane)

Sources & evidence

ORD record: ord-7aee909544e04181bc0d2cf9691208c9
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08138189B2

Reaction notes

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