tert-Butanol → N-[4-(2-carbamoylethyl)cyclohexyl]-N-cyclopropyl-4-[(2S)-1,1,1-trifluoro-2-hydroxypropan-2-yl]benzamide

HRID 1821167Notes

Reaction equation

[C:1]([CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH:8]([N:11]([CH:27]2[CH2:29][CH2:28]2)[C:12](=[O:26])[C:13]2[CH:18]=[CH:17][C:16]([C@@:19]([OH:25])([CH3:24])[C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=2)[CH2:7][CH2:6]1)#[N:2].[OH-].[K+].C([OH:36])(C)(C)C>O>[NH2:2][C:1](=[O:36])[CH2:3][CH2:4][CH:5]1[CH2:6][CH2:7][CH:8]([N:11]([CH:27]2[CH2:28][CH2:29]2)[C:12](=[O:26])[C:13]2[CH:14]=[CH:15][C:16]([C@@:19]([OH:25])([CH3:24])[C:20]([F:21])([F:22])[F:23])=[CH:17][CH:18]=2)[CH2:9][CH2:10]1

Participants

Conditions

Temperature: 85 °C

Procedure

To (S)—N-(4-(2-cyanoethyl)cyclohexyl)-N-cyclopropyl-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzamide prepared above (0.040 g, 0.098 mmol) and KOH (0.55 g, 0.98 mmol) was added tert-butanol (3.75 mL). The mixture was heated to 85° C. and stirred for 15 h. The solution was diluted with water (10 mL) and extracted with 10% MeOH in CH2Cl2 (2×15 mL). The combined organics were dried over Na2SO4 and removed in vacuo. Silica gel chromatography (gradient of 0-10% MeOH in CH2Cl2) afforded (S)—N-(4-(3-amino-3-oxopropyl)cyclohexyl)-N-cyclopropyl-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzamide. 1H NMR (500 MHz, CD3OD): δ 0.45 (bs, 2H), 0.58 (bs, 2H), 1.05-1.15 (m, 2H), 1.27-1.48 (m, 2H), 1.51-1.59 (m, 2H), 1.77 (s, 3H), 1.90-2.00 (m, 5H), 2.25-2.28 (m, 2H), 2.71 (bs, 1H), 4.00 (bs, 1H), 7.52 (d, J=8 Hz, 2H), 7.70 (d, J=8 Hz, 2H).

Workup

extractionextracted with 10% MeOH in CH2Cl2 (2×15 mL)
dry with materialThe combined organics were dried over Na2SO4
customremoved in vacuo

Sources & evidence

ORD record: ord-597ddb1c468d4d99a7094edcbb8f30e9
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07605289B2

Reaction notes

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