Sodium Carbonate → HCID 15454929, compound

HRID 2287536Notes

Reaction equation

HRID 2287536 reaction equation
[NH2:1][C@H:2]1[CH2:7][C@@H:6]([CH2:8][OH:9])[CH2:5][N:4]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[C@H:3]1[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CO[C:28]1[CH:29]=[C:30]([CH:33]=[C:34]([O:36][C:37]([F:40])([F:39])[F:38])[CH:35]=1)[CH:31]=O.[BH-](OC(C)=O)(OC(C)=O)[O:42][C:43](C)=O.[Na+].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH2:13]([O:12][C:10]([N:4]1[CH2:5][C@H:6]([CH2:8][OH:9])[CH2:7][C@H:2]([NH:1][CH2:31][C:30]2[CH:33]=[C:34]([O:36][C:37]([F:38])([F:39])[F:40])[CH:35]=[CH:28][C:29]=2[O:42][CH3:43])[C@@H:3]1[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[O:11])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 15454927HCID 15454927, compoundHCID 18704699HCID 18704699, compound

Product 1

HCID 15454929HCID 15454929, compoundYield 116%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2S*,3S*,5R*)-3-amino-1-benzyloxycarbonyl-5-hydroxymethyl-2-phenylpiperidine (0.405 g, 1.14 mmol) and 3-methoxy-5-trifluoromethoxybenzaldehyde (0.301 g, 1.71 mmol) in dry CH2Cl2 (25.0 ml) was added NaB(OAc)3H (0.362 g, 1.71 mmol) portionwise. The mixture was sonicated to dissolve the NaB(OAc)3H added, and then stirred at room temperature for 2 hours and 40 minutes. To this was added sat. Na2CO3 aq. solution (12.0 ml), and the CH2Cl2 layer was separated. The aqueous layer was extracted with CH2Cl2. The combined CH2Cl2 layer and extracts were dried (K2CO3), and concentrated in vacuo to give a pale yellow oil (0.72 g). This was flash chromatographed over SiO2 (Merch Kieselgel 60, 14.0 g). Elution with CH2Cl2 --MeOH (300:1/200:1/100:1) gave title compound [0.416 g, overall 67.0% from (2S*,3S*,5R*)-1-benzyloxycarbonyl-3-(N-tert-butoxy-carbonyl)amino-5-hydroxymethyl-2-phenylpiperidine in two steps] as a colorless syrup. IRmax (film): 3450(s), 1700(s), 1682(s), 1670(s), 1652(s), 1610(w), 1497(s), 1490(s), 1260(br., s), 1220(br., s), 1152(br., s), 1030(s), 738(s), 700(s) cm-1 ; 1H-NMR δ: 7.50-7.11(m, 10H), 7.13-6.93(m, 1H), 6.69(br.d, J=8.4 Hz, 1H), 5.60-5.22(m, 1H), 5.20-4.95(m, 2H), 4.36-4.10(m, 1H), 3.79(d, J=13.9 Hz, 1H), 3.65-3.45(m, 3H), 3.59(br.s, 3H), 3.23-2.95(m, 2H), 2.15(br.s, 1H), 2.02-1.86(m, 1H), 1.86-1.68(m, 1H), 1.68-1.45)m, 2H) ppm.

Workup

  1. customThe mixture was sonicated
  2. additionadded
  3. customthe CH2Cl2 layer was separated
  4. extractionThe aqueous layer was extracted with CH2Cl2
  5. dry with materialThe combined CH2Cl2 layer and extracts were dried (K2CO3)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8cc5a479fc914949a497469aa8aa3842
Source dataset
uspto-grants-2000_07
Patent number
US06083943

Reaction notes

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