(2S)-2-Amino-N,3,3-trimethylbutanamide → 3(R)-(t-butoxycarbonylamino)-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid allyl ester

HRID 566758Notes

Reaction equation

HRID 566758 reaction equation
[CH2:1]([O:8][C:9](=[O:32])[CH2:10][C@@H:11]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][CH3:22])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:13])[C:2]1C=CC=C[CH:3]=1.C(OC(=O)[C@@H](CC([O-])=O)NC(OC(C)(C)C)=O)(=C)C.CNC(=O)[C@H](C(C)(C)C)N.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>>[CH2:1]([O:8][C:9](=[O:32])[CH2:10][C@@H:11]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:12]([NH:14][C@H:15]([C:20](=[O:23])[NH:21][CH3:22])[C:16]([CH3:19])([CH3:18])[CH3:17])=[O:13])[CH:2]=[CH2:3]

Participants

5

Reactant 4

HCID 445856(2S)-2-Amino-N,3,3-trimethylbutanamideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 537065323(R)-t-butoxycarbonylamino-N-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)succinamic acid benzyl esterHCID 131722275beta-allyl-N-t-butoxycarbonyl-D-aspartate

Product 1

HCID 544245593(R)-(t-butoxycarbonylamino)-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid allyl esterYield 84%

Procedure

According to Example 1(b) for 3(R)-t-butyloxycarbonylamino-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid benzyl ester, β-allyl-N-t-butoxycarbonyl-D-aspartate (Belshaw, P.; Mzengeza, S.; Lajoie, G. Syn Commun 1990, 20, 3157-3160; 2.00 g, 7.32 mmol) and L-t-leucine N-methylamide (Malon, P.; Pancoska, P.; Budesinsky, M.; Hlavacek, J.; Pospisek, J.; Blaha, K. Coll. Czech. Chem Commun. 1983, 48, 2844-2861; 1.05 g, 7.32 mmol) were coupled with TBTU. The resultant yellow oil was routinely used without further purification. Flash column chromatography with 2% MeOH/CH2Cl2 provided 2.44 g (84%) of 3(R)-(t-butoxycarbonylamino)-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid allyl ester as a pale yellow oil. 1H NMR (CDCl3): δ 7.05 (d, 1H, J=9.0 Hz), 5.98 (d, 1H, J=4.4 Hz), 5.77 (ddt, 1H, J=5.6, 10.3, 16.2 Hz), 5.29 (ddd, 1H, J=1.5, 2.8, 15.6 Hz), 5.23 (dd, 1H, J=1.3, 10.5 Hz), 4.57 (dddd, 2H, J=1.6, 3.1, 5.6, 12.1 Hz), 4.11 (d, 1H, J=9.4 Hz), 2.77 (d, 3H, J=5.0 Hz), 1.46 (s, 9H), 0.99 (s, 9H).

Workup

  1. customThe resultant yellow oil was routinely used without further purification

Sources & evidence

ORD record
ord-3e91ec03835d4a8e84bbe91357ab8e89
Source dataset
uspto-grants-2001_01
Patent number
US06174915B1

Reaction notes

Loading…