O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → 3(R)-t-butoxycarbonylamino-N-(2hydroxy-1-(S)-hydroxymethyl-2-methylpropyl)succinamic acid benzyl ester

HRID 2299929Notes

Reaction equation

HRID 2299929 reaction equation
Cl.N[C@@H:3]([C:6]([CH3:9])([OH:8])[CH3:7])CO.C[N:11]([C:13]([O:17]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:32]([O:39][C:40](=[O:61])[C@H:41](NC(OC(C)(C)C)=O)[CH2:42][C:43]([NH:45][C@@H:46]([CH2:51][OH:52])[C:47]([OH:50])([CH3:49])[CH3:48])=[O:44])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>>[CH2:32]([O:39][C:40](=[O:61])[CH2:41][C@@H:42]([NH:11][C:13]([O:8][C:6]([CH3:3])([CH3:7])[CH3:9])=[O:17])[C:43]([NH:45][C@@H:46]([CH2:51][OH:52])[C:47]([OH:50])([CH3:48])[CH3:49])=[O:44])[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

4

Reactant 3

HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 18341280(2R)-2-amino-3-methylbutane-1,3-diol hydrochlorideHCID 70158189(r)-t-Butoxycarbonylamino-n-[2-hydroxy-1(s)-(hydroxymethyl)-2-methylpropyl]succinamic acid benzyl ester

Product 1

HCID 538878773(R)-t-butoxycarbonylamino-N-(2hydroxy-1-(S)-hydroxymethyl-2-methylpropyl)succinamic acid benzyl esterYield 52%

Procedure

3-Benzyloxycarbonyl-2,2-dimethyl-4R-(1-hydroxy-1-methyl-ethyl)-oxazolidine was hydrogenolyzed in the presence of HCl according to conditions described in Example 1(a) to provide crude 2(R)-amino-3-methyl-butane-1,3-diol hydrochloride. According to the procedure described in Example 1(b) for the preparation of 3(R)-t-butoxycarbonylamido-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid benzyl ester, the crude amine salt was coupled to N-t-butoxycarbonyl-D-aspartic acid β-benzyl ester with TBTU. Purification via column chromatography with EtOAc/CH2Cl2 (1:1) to 10% MeOH/CH2Cl2 gradient elution led to isolation in 52% yield of 3 (R)-t-butoxycarbonylamino-N-[2-hydroxy-1(S)-(hydroxymethyl)-2-methylpropyl]succinamic acid benzyl ester, which was used without further purification. 1H NMR (CD3CN): δ 7.51 (s, 5H), 6.99 (bs, 1H), 5.99 (bs, 1H), 5.25 (s, 2H), 4.57-4.50 (m, 1H), 3.83-3.76 (m, 3H), 3.00 (dd, 1H, J=5.7, 16.4 Hz), 2.87 (dd, 1H, J=7.2, 16.6 Hz), 1.55 (s, 9H), 1.34 (s, 3H), 1.22 (s, 3H). Anal. Calculated for C21H32N2O7.0.5 H2O.0.1 O═C[N-(CH3)2]2: C, 58.02; H, 7.74; N, 6.92. Found: C, 58.29; H, 7.75; N, 6.82.

Workup

  1. customPurification via column chromatography with EtOAc/CH2Cl2 (1:1)
  2. washto 10% MeOH/CH2Cl2 gradient elution

Sources & evidence

ORD record
ord-6077f447db3e491e9b0ad9a3a3ce94f7
Source dataset
uspto-grants-2002_12
Patent number
US06495699B2

Reaction notes

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