Formic Acid → Isopropyl-methyl-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]-tetrahydropyran-4-ylmethyl}amine

HRID 272881Notes

Reaction equation

[CH:1]([NH:4][CH2:5][C:6]1([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1)([CH3:3])[CH3:2].C=O.[CH:29](O)=O.O>C(OCC)(=O)C>[CH:1]([N:4]([CH3:29])[CH2:5][C:6]1([C:12]2[CH:13]=[CH:14][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]3[CH2:23][CH2:24][CH2:25][CH2:26]3)=[CH:16][CH:17]=2)[CH2:7][CH2:8][O:9][CH2:10][CH2:11]1)([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

To isopropyl-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-ylmethyl}-amine (258 mg, 0.71 mmol) was added formaldehyde (37% w/w solution in H2O, 1 mL) and formic acid (1.5 mL). The resulting mixture was heated to 60° C. overnight. After cooling, H2O and ethyl acetate were added. The aqueous layer was separated, basified with 30% NaOH and extracted 3 times with ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo to give the title compound as an oil (170 mg, 65%). 1H NMR (400 MHz, CDCl3) δ 7.19 (d, 2H), 6.86 (d, 2H), 4.02 (t, 2H), 3.76 (m, 2H), 3.50 (m, 2H), 2.63 (t, 2H), 2.53 (m, 4H), 2.44 (m, 1H), 2.38 (s, 2H), 2.08 (m, 2H), 2.01 (m, 2H), 1.89 (m, 2H), 1.85 (s, 3H), 1.79 (m, 4H), 0.84 (d, 6H).

Workup

temperatureAfter cooling
customThe aqueous layer was separated
extractionextracted 3 times with ethyl acetate
dry with materialThe combined organic extracts were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-cf504738b4e4446dbf56d437cfd5216a
Source dataset: uspto-grants-2008_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07456164B2

Reaction notes

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