Hydrochloric Acid → (1S)-4-amino-N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]1-isopropylcyclopent-2-ene-1-carboxamide

HRID 643528Notes

Reaction equation

[C:1]([O:5][C:6]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][C:7]=1[CH2:8][NH:9][C:10]([C@:12]1([CH:24]([CH3:26])[CH3:25])[CH2:16][CH:15]([N:17]2C(C)=CC=C2C)[CH:14]=[CH:13]1)=[O:11])([CH3:4])([CH3:3])[CH3:2].Cl.ON.[OH-].[Na+]>CO.O.CCOC(C)=O>[NH2:17][CH:15]1[CH2:16][C@@:12]([CH:24]([CH3:26])[CH3:25])([C:10]([NH:9][CH2:8][C:7]2[CH:27]=[C:28]([C:31]([F:33])([F:34])[F:32])[CH:29]=[CH:30][C:6]=2[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:11])[CH:13]=[CH:14]1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of (1S)—N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-isopropylcyclopent-2-ene-1-carboxamide (46 g, 97 mmol),hydroxyanime HCl (41 g, 580 mmol), and hydroxyamine (50% in H2O, 50 mL) in MeOH:H2O (2:1, 450 mL) was heated to 70° C. for 11 hr until no more starting material left as judged by HPLC. The reaction mixture was then cooled to r. t., the pH was adjusted to 11.0 with 1 N NaOH, and it was diluted with EtOAc. The aqueous phase was then extracted with EtOAc (5×). The organics were then combined, dried over sodium sulfate and evaporated to dryness to give 35 g of (1S)-4-amino-N-[2-tert-butoxy-5-(trifluoromethyl)benzyl]-1-isopropylcyclopent-2-ene-1-carboxamide as a yellow oil that crystallized upon standing.

Workup

waitleft
temperatureThe reaction mixture was then cooled
extractionThe aqueous phase was then extracted with EtOAc (5×)
dry with materialdried over sodium sulfate
customevaporated to dryness

Sources & evidence

ORD record: ord-9cc1199f87c14d5e95cc2d315ad7cd47
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07700591B2

Reaction notes

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