Triethylamine → di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-[3-tert-butoxy-4-(2-fluoroethoxy)benzyl]-L-glutamate

HRID 591327Notes

Reaction equation

HRID 591327 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:10][C@H:11]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28]O)=[C:22]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:21]=1)[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:42]C(F)(F)C(F)(F)C(F)(F)C(F)(F)S(F)(=O)=O.F.F.F.C(N(CC)CC)C.C(N(CC)CC)C>C1COCC1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:10][C@H:11]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][CH2:28][F:42])=[C:22]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:21]=1)[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 67814Perfluoro-1-butanesulfonyl fluoride2×HCID 175505N,N-Diethylethanamine trihydrofluoride2×HCID 117812680di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-[3-tert-butoxy-4-(2-hydroxyethoxy)benzyl]-L-glutamate

Product 1

HCID 117812704di-tert-butyl (4S)-N-(tert-butoxycarbonyl)-4-[3-tert-butoxy-4-(2-fluoroethoxy)benzyl]-L-glutamateYield 37.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 64 mg (0.11 mmol) di-tert-butyl (4S)—N-(tert-butoxycarbonyl)-4-[3-tert-butoxy-4-(2-hydroxyethoxy)benzyl]-L-glutamate in 0.5 ml THF was added 102.7 mg (0.34 mmol) nonafluoro 1-butanesulphonic acid fluoride, 54.8 mg (0.34 mmol) triethylamine trihydrofluoride and 102 mg (1.01 mmol) triethyl amine. The reaction mixture is stirred for 3 days. Further 34 mg (0.11 mmol) nonafluoro 1-butanesulphonic acid fluoride, 18 mg (0.11 mmol) triethylamine trihydrofluoride and 34 mg (0.33 mmol) triethyl amine were added. The reaction mixture is stirred for 3 hours and is concentrated in vacuo. The crude product is purified by column chromatography (silica gel, hexane/ethylacetate gradient: 12:1→1:1). The desired product was obtained in 37.4% yield (64.2 mg, 0.04 mmol).

Workup

  1. stirringThe reaction mixture is stirred for 3 hours
  2. concentrationis concentrated in vacuo
  3. customThe crude product is purified by column chromatography (silica gel, hexane/ethylacetate gradient: 12:1→1:1)

Sources & evidence

ORD record
ord-f0b1f16768e3421e894191d005cf75d0
Source dataset
uspto-grants-2016_01
Patent number
US09238631B2

Reaction notes

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