Diisopropylethylamine → HCID 460961, compound

HRID 963576Notes

Reaction equation

HRID 963576 reaction equation
[NH2:1][C@H:2]([C@@H:10]([OH:28])[CH2:11][C@@H:12]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[OH:29][C:30]1[C:31]([CH3:39])=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33](O)=[O:34].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.NCCN1CCOCC1>CN(C)C=O>[OH:29][C:30]1[C:31]([CH3:39])=[C:32]([C:33]([NH:1][C@H:2]([C@@H:10]([OH:28])[CH2:11][C@@H:12]([NH:20][C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:3][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:34])[CH:36]=[CH:37][CH:38]=1

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 2520233-Hydroxy-2-methylbenzoic AcidHCID 4082852-MorpholinoethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27960291-Hydroxybenzotriazole hydrateHCID 119979265-tert-Butyloxycarbonylamino-2-amino-3-hydroxy-1,6-diphenylhexane, (2S,3S,5S)-

Product 1

HCID 460961HCID 460961, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound (2S,3S,5S)-2-[N-[(3-hydroxy-2-methylphenyl)carbonyl]amino]-5-[N-(tert-butyloxycarbonyl)amino]-1,6-diphenyl-3-hydroxy hexane (RS-208) was prepared from RS-216. A solution of (2S,3S,5S)-2-amino-5-[N-(tert-butyloxycarbonyl)amino]-1,6-diphenyl-3-hydroxy hexane (RS-216, 1.1 g, 2.86 mmol), 3-hydroxy-2-methyl-benzoic acid (0.478 g, 3.2 mmol), O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TBTU, 1.02 g, 3.2 mmol), 1-hydroxybenzotriazole hydrate (HOBT, 0.919 g, 6.0 mmol) and diisopropylethylamine (DIPEA, 103 ml, 6.0 mmol) in dimethylformamide (DMF, 30 ml) was stirred at room temperature for 2 h. After addition of aminoethyl morpholine (50 ml) the solvents were removed under vacuum and the residue was diluted with ethyl acetate and washed sequentially with aqueous NaHCO3, aqueous KHSO4, brine, then dried on Na2SO4, and concentrated in vacuo. Solid was suspended in ethyl acetate, filtered and residue was washed with ethyl acetate. Crystallization from ethyl acetate:methanol:hexane (1:0.2:1.5) provided 1.4 g (94%) of white solid; mp=162°-163° C.; TLC [Rf =0.75 (ethyl acetate:hexane, 7:3)]; HPLC rt=19.5 min; MS m/z 519 (M+H)+ ; 1H NMR.

Workup

  1. customwere removed under vacuum
  2. additionthe residue was diluted with ethyl acetate
  3. washwashed sequentially with aqueous NaHCO3, aqueous KHSO4, brine
  4. customdried on Na2SO4
  5. concentrationconcentrated in vacuo
  6. filtrationfiltered
  7. washresidue was washed with ethyl acetate
  8. customCrystallization from ethyl acetate:methanol:hexane (1:0.2:1.5)

Sources & evidence

ORD record
ord-e830509aea6943678890e38f2e984005
Source dataset
uspto-grants-1998_06
Patent number
US05763464

Reaction notes

Loading…