tert-Butyl ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamate → tert-butyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-bromo-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate

HRID 501742Notes

Reaction equation

HRID 501742 reaction equation
C(O[C@H]1C2C(=CC(OCCC)=CC=2)[C@@H](N)C1)C=C.[CH2:19]([O:22][C@H:23]1[C:31]2[C:26](=[CH:27][C:28]([Br:32])=[CH:29][CH:30]=2)[C@@H:25]([NH2:33])[CH2:24]1)[CH:20]=[CH2:21].[F:34][C:35]1[CH:36]=[C:37]([CH2:42][C@H:43]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[C@H:44]2[CH2:46][O:45]2)[CH:38]=[C:39]([F:41])[CH:40]=1>>[CH2:19]([O:22][C@H:23]1[C:31]2[C:26](=[CH:27][C:28]([Br:32])=[CH:29][CH:30]=2)[C@@H:25]([NH:33][CH2:46][C@@H:44]([OH:45])[C@@H:43]([NH:47][C:48](=[O:54])[O:49][C:50]([CH3:52])([CH3:51])[CH3:53])[CH2:42][C:37]2[CH:36]=[C:35]([F:34])[CH:40]=[C:39]([F:41])[CH:38]=2)[CH2:24]1)[CH:20]=[CH2:21]

Participants

4

Reactant 3

HCID 9922319tert-Butyl ((S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethyl)carbamateHCID 59423731(1S,3R)-3-(Allyloxy)-6-bromo-2,3-dihydro-1H-inden-1-amineHCID 59423826(1S,3R)-3-(Allyloxy)-6-propoxy-2,3-dihydro-1H-inden-1-amine2×

Product 1

HCID 59423828tert-butyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-bromo-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamateYield 76%

Procedure

Step BE (1). (1S,3R)-3-(Allyloxy)-6-bromo-2,3-dihydro-1H-inden-1-amine from Step Z(1) was reacted with tert-butyl (S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethylcarbamate following a procedure analogous to Step AW (1) to afford 1.5 g (76% yield) of tert-butyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-bromo-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate. LC-MS (M+H)+ 568.97. 1H NMR (300 MHz, CDCl3) δ ppm 1.35 (s, 9H) 1.79-1.90 (m, 2H) 2.64-2.82 (m, 4H) 3.03 (dd, J=14.09, 4.21 Hz, 1H) 3.36-3.44 (m, 1H) 3.68-3.80 (m, J=8.42, 4.03 Hz, 1H) 4.01-4.12 (m, 3H) 4.50 (d, J=9.51 Hz, 1H) 4.73 (t, J=6.04 Hz, 1H) 5.18 (dd, J=10.43, 1.28 Hz, 1H) 5.24-5.34 (m, J=17.20, 1.46 Hz, 1H) 5.92 (ddd, J=22.60, 10.52, 5.67 Hz, 1H) 6.63 (tt, J=9.01, 2.33 Hz, 1H) 6.70-6.78 (m, 2H) 7.25 (d, J=8.05 Hz, 1H) 7.39 (dd, J=7.87, 1.65 Hz, 1H) 7.49 (s, 1H).

Sources & evidence

ORD record
ord-f1001d2eec12464e9ed8e14265b8c697
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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