Carbamate → tert-butyl (S)-2-(4-(4-(thiophen-3-yl)phenethyloxy)phenylcarbamoyl)-1-hydroxypropan-2-ylcarbamate

HRID 1295517Notes

Reaction equation

HRID 1295517 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][OH:14])=[CH:8][CH:7]=2)=[CH:2]1.[C:15]([NH:22][C@:23]([CH3:29])([C:26]([OH:28])=O)[CH2:24][OH:25])([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].CN(C(ON1N=N[C:40]2[CH:41]=[CH:42][CH:43]=[N:44][C:39]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.P([O-])([O-])([O-])=O.[C:59](=O)([O-])N>CCN(C(C)C)C(C)C>[S:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][O:14][C:40]3[CH:39]=[CH:59][C:43]([NH:44][C:26]([C@:23]([NH:22][C:15](=[O:16])[O:17][C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:29])[CH2:24][OH:25])=[O:28])=[CH:42][CH:41]=3)=[CH:8][CH:7]=2)=[CH:2]1

Participants

7

Reactant 5

HCID 276CarbamateHCID 1061PhosphateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12991620(S)-2-((tert-Butoxycarbonyl)amino)-3-hydroxy-2-methylpropanoic acidHCID 691144792-(4-(Thiophen-3-yl)phenyl)ethanol

Product 1

HCID 86605704tert-butyl (S)-2-(4-(4-(thiophen-3-yl)phenethyloxy)phenylcarbamoyl)-1-hydroxypropan-2-ylcarbamateYield 24.2%

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Procedure

The starting material, 2-(4-(thiophen-3-yl)phenyl)ethanol, was synthesized as follows: In a sealed vessel was combined 2-(4-bromophenyl)ethanol (70 μL), 4,4,5,5-tetramethyl-2-(thiophen-3-yl)-1,3,2-dioxaborolane (126 mg), K2CO3 (207 mg), catalytic Pd(PPh3)4, 4.5 mL THF, and 0.5 mL H2O. The vessel was heated in an oil bath at 60° C. overnight. The reaction mixture was diluted with water and DCM. The organic layer was concentrated to yield 2-(4-(thiophen-3-yl)phenyl)ethanol (80 mg) as a solid white product. 80 mg tert-butyl (S)-2-(4-(4-(thiophen-3-yl)phenethyloxy)phenylcarbamoyl)-1-hydroxypropan-2-ylcarbamate was synthesized following the general procedure employing 2-(4-(thiophen-3-yl)phenyl)ethanol (200 mg), N-(Boc)-α-methylserine (175 mg), HATU (375 mg), and DIPEA (430 uL). MS (ESI, M+Na+)=519. 2.6 mg of the phosphate was then synthesized from the carbamate (40 mg) as a solid white solid. MS (ESI, M+H+)=477; 1H NMR (400 MHz, DMSO-d6), 9.96 (br s, 1H), 7.81 (m, 1H), 7.65 (m, 3H), 7.5 (m, 3H), 7.3 (m, 2H), 6.9 (m, 2H), 4.28 (m, 1H), 4.17 (m, 2H), 4.06 (m, 1H), 3.04 (t, 2H), 1.48 (s, 3H).

Sources & evidence

ORD record
ord-f91243c843f843bc918ee9642fe353d5
Source dataset
uspto-grants-2007_07
Patent number
US07241812B2

Reaction notes

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