Tetrabutylammonium Fluoride → (2-chloro-7-cycloheptyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)methanol

HRID 1850523Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH:9]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[C:5]([C:16]#[C:17][CH2:18][OH:19])=[CH:4][N:3]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:16]=[C:17]([CH2:18][OH:19])[N:8]([CH:9]3[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]3)[C:6]=2[N:7]=1

Participants

Conditions

Temperature: 63 °C

Procedure

To a suspension of 3-(2-chloro-4-(cycloheptylamino)pyrimidin-5-yl)prop-2-yn-1-ol (8.64 g, 30.9 mmol) in THF (200 mL) was added a solution of TBAF in THF (1M, 66 mL, 2.1 equiv) and the resulting mixture was heated at 63° C. for 5 h. The reaction mixture was concentrated to remove THF, diluted with EtOAc (350 mL), washed with water (140 mL) and brine (140 mL), dried over Na2SO4, filtered and concentrated. Trituration of the residue using iPrOH, CH2Cl2, and MeCN followed by column chromatography of the mother liquor (EtOAc/heptane 20 to 100%) provided (2-chloro-7-cycloheptyl-7H-pyrrolo[2,3-d]pyrimidin-6-yl)methanol (6.24 g) in 72% yield. 1H NMR (400 MHz, CDCl3) δ 8.69 (s, 1H), 6.45 (s, 1H), 4.83 (s, 2H), 4.61 (m, 1H), 2.54 (m, 2H), 1.98-1.86 (m, 4H), 1.73-1.55 (m, 6H); MS m/z 280.4 (M+H)+

Workup

concentrationThe reaction mixture was concentrated
customto remove THF
additiondiluted with EtOAc (350 mL)
washwashed with water (140 mL) and brine (140 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-2210e6e9dd7f4722bc80fe0882f225aa
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08957074B2

Reaction notes

Loading…