Hydrochloric Acid → HCID 58005171, compound

HRID 1879263Notes

Reaction equation

HRID 1879263 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[Cl-].[Br:51][C:52]1[CH:53]=[C:54]([C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([CH2:64][O:65][C@H:66]3[CH2:70][NH2+:69][C@H:68]([C:71]([O:73][CH3:74])=[O:72])[CH2:67]3)[CH:59]=2)[CH:55]=[CH:56][CH:57]=1.Cl>CN(C=O)C.CCOC(C)=O.O>[Br:51][C:52]1[CH:53]=[C:54]([C:58]2[CH:63]=[CH:62][CH:61]=[C:60]([CH2:64][O:65][C@H:66]3[CH2:70][N:69]([C:10](=[O:12])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH:13]4[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]4)[C@H:68]([C:71]([O:73][CH3:74])=[O:72])[CH2:67]3)[CH:59]=2)[CH:55]=[CH:56][CH:57]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7004938N-(tert-Butoxycarbonyl)-L-cyclohexylglycineHCID 86637108HCID 86637108, compound

Product 1

HCID 58005171HCID 58005171, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2S)-[(tert-butoxycarbonyl)amino](cyclohexyl)acetic acid (1.05 eq.), DIPEA (3.2 eq.) and TBTU (1.1 eq.) were added to a 0.12M solution of methyl (4R)-4-[(3′-bromobiphenyl-3-yl)methoxy]-L-prolinate hydrochloride 97 in DMF. The reaction mixture was stirred at RT for 2 h then it was diluted with EtOAc:H2O and acidified with aqueous (1N) HCl. The phases were separated and the organic layer was washed sequentially with aqueous (1N) HCl, aqueous (2N) NaOH and brine, dried (Na2SO4) and evaporated under reduced pressure to afford the title compound 106 (95% crude yield) as a pale yellow foam which was used without further purification. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 7.86 (s, 1H), 7.70 (d, J 7.8, 1H), 7.66-7.57 (m, 3H), 7.54-7.33 (m, 3H), 6.94 (d, J 8.6, 1H), 4.65 (d, J 11.6, 1H), 4.58 (d, J 11.6, 1H), 4.36 (t, J 8.5, 1H), 4.32 (bs, 1H), 4.19 (d, J 11.1, 1H), 4.11 (t, J 11.1, 1H), 3.74-3.66 (m, 1H), 3.65 (s, 3H), 2.48-2.35 (m, 1H), 2.08-1.97 (m, 1H), 1.83-1.55 (m, 6H), 1.44-1.37 (m, 1H), 1.34 (s, 9H), 1.22-1.09 (m, 2H), 1.08-0.93 (m, 2H). MS (ES+) m/z 629, 631 (M+H)+

Workup

  1. customThe phases were separated
  2. washthe organic layer was washed sequentially with aqueous (1N) HCl, aqueous (2N) NaOH and brine
  3. dry with materialdried (Na2SO4)
  4. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-c0ce7694a84f42618a198049c8f00dd4
Source dataset
uspto-grants-2012_11
Patent number
US08314062B2

Reaction notes

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